About MUTYH
No gene-level summary was recorded for this case.
Previous versions
Variant interpretation report
MUTYH c.995C>T, p.(Ser332Leu)
Classification
Uncertain significance
Variant description:
No variant summary was recorded for this case.
Five-step scale from benign to pathogenic. This variant is uncertain. Select a step to read what it means.
Uncertain.The recorded classification is uncertain significance.
In plain language
Gene-level background from the recorded interpretation.
Words with a dotted underline have a short definition. Hover or tap them.
LYFE Sciences is an AI system, and it can make mistakes.
Criteria may be applied incorrectly, sources may be misread, and a
confident-looking classification can still be wrong.
Double-check every criterion and its underlying evidence
before relying on any call.
01The reasoning
How it was classified
The recorded framework is ClinGen MUTYH VCEP v1.0.0. The criteria and strengths shown below come from the saved assessment; this page does not recalculate the classification.
Recorded applied criteria
The applied criteria and their strengths are shown as assessed under the stated framework.
Pathogenic evidence criteria: 1
Benign evidence criteria: 1
Pathogenic criteria applied · 1
PM2Supporting
PM2 · supporting
NM_001048171.1:c.995C>T is present at very low frequency in population databases. gnomAD v2.1 reports 14 heterozygotes among 273,222 alleles (AF=0.00512%, 0 homozygotes); gnomAD v4.1 reports 56 heterozygotes among 1,609,824 alleles (AF=0.00348%, 0 homozygotes). Both allele frequencies are below the 0.1% PM2 threshold. The variant is absent from gnomAD-Canada.
Benign criteria applied · 1
BP4Supporting
BP4 · supporting
Multiple lines of computational evidence suggest that this missense variant has no impact on gene product function. The REVEL score is 0.116 (below 0.5), BayesDel score is -0.476 (predicting benign), and SpliceAI predicts no splicing alteration (max delta = 0.00). All three in silico tools concordantly predict a benign effect.
Recorded classification: Uncertain significance
InSiGHT Hereditary Colorectal Cancer/Polyposis Specification v1.0.0 lacked a usable explicit final combination framework, so generic ACMG/AMP 2015 final-combination rules were applied as fallback; applied criteria: PM2 supporting, BP4 supporting benign; combination = 1 supporting + 1 supporting benign, which maps to VUS.
02The sources
Evidence at a glance
Evidence summaries and captured source records, where available. Missing entries should not be interpreted as negative findings.
gnomAD v4.1
gnomAD v2.1
Population frequency
56 / 1,609,824 alleles
gnomAD v4.1: 56 / 1,609,824 alleles. Recorded AF 3.47864e-05. Recorded homozygote count 0.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 5.12404e-05; MAF= 0.00512%, 14/273222 alleles, homozygotes = 0) and has highest observed frequency in the South Asian population (AF= 0.000365764; MAF= 0.03658%, 11/30074 alleles, homozygotes = 0); grpmax FAF= 0.00020417.
SpliceAI score
0.000 maximum delta
Recorded SpliceAI maximum delta score: 0.000. Refer to the recorded PP3/BP4 rationale for interpretation.
ClinVar submissions
9 reported laboratory submissions
7 Uncertain significance · 1 Likely benign · 1 Uncertain Significance.
Context only
ClinVar ↗
Functional evidence
Statement recorded
OncoKB did not identify variant-specific reviewed functional evidence for this variant; gene-level curated context is available for reviewer follow-up. MUTYH, a DNA glycosylase, is frequently mutated in colorectal cancer.
No listed criterion applied
OncoKB ↗
COSMIC
Cancer Hotspots
Somatic evidence
No matching record reported
This variant has not previously been reported in somatic cancers (COSMIC).
Cancer Hotspots
This variant does not lie in a statistically significant hotspot.
Context only
For specialists
Technical detail
ACMG/AMP criteria under ClinGen MUTYH VCEP v1.0.0, with the data and sources behind each one.
29 criteria with recorded statuses: 2 met · 17 not met · 4 not assessed · 6 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.
Met
Not met
Not assessed
Not applicable
NM_001048171.1:c.995C>T (p.Ser332Leu) is a missense variant in exon 12 of MUTYH, a gene associated with autosomal recessive MUTYH-associated polyposis (MAP).
The variant is present at very low frequency in gnomAD (v2.1 AF=0.00512%; v4.1 AF=0.00348%), with no homozygous observations, consistent with PM2 supporting evidence.
Multiple in silico prediction tools concordantly predict a benign effect: REVEL score 0.116 (below 0.5 threshold), BayesDel score -0.476 (predicting benign), and SpliceAI predicts no splicing impact (max delta 0.00). This supports BP4 criteria.
ClinVar submissions predominantly classify this variant as Uncertain significance (7/11 submitters). One clinical laboratory (Ambry Genetics) classifies it as Likely benign. No expert panel classification has been issued.
Functional evidence from D'Agostino et al. 2009 (PMID:19092703) suggesting reduced glycosylase activity for p.S332L was identified through exploratory search but could not be independently verified as full-text was not available in the case materials. This evidence was not applied.
Overall, one supporting pathogenic criterion (PM2) and one supporting benign criterion (BP4) are met, placing this variant in the VUS (Variant of Uncertain Significance) category under generic ACMG/AMP 2015 combination rules.
No criteria match.
Met · 2
PM2 SupportingNM_001048171.1:c.995C>T is present at very low frequency in population databases. gnomAD v2.1 reports 14 heterozygotes among 273,222 alleles (AF=0.00512%, 0 homozygotes); gnomAD v4.1 reports 56 heterozygotes among 1,609,824 alleles (AF=0.00348%, 0 homozygotes). Both allele frequencies are below the 0.1% PM2 threshold. The variant is absent from gnomAD-Canada. Details ▾Hide ▴
Evidence considered
- gnomAD v2.1: AF=0.00512% (14/273
- 222 alleles
- 0 homozygotes).
- gnomAD v4.1: AF=0.00348% (56/1
- 609
- 824 alleles
- gnomAD-Canada: Absent.
- Highest subpopulation frequency: South Asian
- 0.0366% (v2.1) / 0.0452% (v4.1)
- still below 0.1%.
Sources
BP4 SupportingMultiple lines of computational evidence suggest that this missense variant has no impact on gene product function. The REVEL score is 0.116 (below 0.5), BayesDel score is -0.476 (predicting benign), and SpliceAI predicts no splicing alteration (max delta = 0.00). All three in silico tools concordantly predict a benign effect. Details ▾Hide ▴
Evidence considered
- REVEL: 0.116 (benign
- below 0.5 threshold).
- BayesDel: -0.475899 (negative score
- consistent with benign).
- SpliceAI: max delta score 0.00 (no splicing impact).
- All three prediction tools concordantly indicate a benign effect.
Sources
Not met · 17 · evaluated, threshold not reached
PS1 No established pathogenic variant at the same amino acid position (p.S332) with the same change (Ser332Leu) has been identified in ClinVar or the literature. PS1 requires an identical amino acid change in a known pathogenic variant. Details ▾Hide ▴
Evidence considered
- ClinVar does not list any pathogenic variant with the identical S332L change.
- PM5 candidate review found no same-residue comparator variants with established pathogenicity.
Sources
clinvar ↗pm5_candidates
PS2 No de novo observation with confirmed paternity and maternity has been reported for this variant in ClinVar or the literature. MUTYH-associated polyposis is autosomal recessive, making de novo presentations unlikely to manifest phenotypically. Details ▾Hide ▴
Evidence considered
- ClinVar submissions (11 total) contain no reports of de novo occurrence.
- Exploratory literature search confirmed absence of de novo observations.
Still missing
- No de novo testing data available
- unlikely to be pursued for a recessive-condition missense variant.
Sources
PS4 No case-control study has demonstrated statistically significant enrichment of NM_001048171.1:c.995C>T in affected individuals versus controls. The variant is observed in gnomAD at low frequency, but population frequency alone does not establish case enrichment. MUTYH-associated polyposis is autosomal recessive, further complicating PS4 assessment for monoallelic observations. Details ▾Hide ▴
Evidence considered
- gnomAD v2.1: 14/273
- 222 alleles (AF=0.00512%).
- gnomAD v4.1: 56/1
- 609
- 824 alleles (AF=0.00348%).
- No published case-control study with odds-ratio data for this variant.
Still missing
- No dedicated case-control study for c.995C>T in MUTYH-associated polyposis.
Sources
PM5 No pathogenic missense variant at the same residue (p.Ser332) with a different amino acid change has been identified. The PM5 candidate harvest found zero same-residue comparator candidates meeting the governing PM5 rule. Details ▾Hide ▴
Evidence considered
- PM5 candidate harvest returned no same-residue pathogenic comparator variants at p.S332.
Sources
pm5_candidates
PM6 No assumed de novo observation (without confirmed paternity/maternity) has been reported for this variant. MUTYH-associated polyposis is autosomal recessive; PM6 is rarely applicable in recessive cancer predisposition genes. Details ▾Hide ▴
PP1 No cosegregation data are available for NM_001048171.1:c.995C>T. No family-based segregation study including this variant has been published or is recorded in major databases. Details ▾Hide ▴
Evidence considered
- Exploratory literature and database search found no cosegregation data for this variant.
Still missing
- No published family studies with this variant.
PP2 While MUTYH is a gene in which missense variants are a known disease mechanism for MUTYH-associated polyposis, PP2 under generic ACMG/AMP 2015 requires that the gene have a low rate of benign missense variation. MUTYH tolerates missense variation in the general population (numerous missense variants with AF>0.1% in gnomAD), precluding application of PP2. Details ▾Hide ▴
Evidence considered
- MUTYH missense variants are common in gnomAD with many exceeding the benign AF threshold
- indicating the gene tolerates missense variation.
- PP2 is reserved for genes with a low rate of benign missense variation.
Sources
PP3 Multiple in silico prediction tools suggest a benign impact of this missense change. REVEL score is 0.116 (below the 0.5 threshold), BayesDel score is -0.476 (negative, predicting benign), and SpliceAI predicts no splicing impact (max delta score = 0.00). No computational tool supports a deleterious effect, so PP3 is not met. Details ▾Hide ▴
Evidence considered
- REVEL: 0.116 (below 0.5 damaging threshold).
- BayesDel: -0.475899 (negative score
- predicts benign).
- SpliceAI: max delta 0.00 (no splicing impact predicted).
Sources
PP5 No reputable source has classified NM_001048171.1:c.995C>T as pathogenic. ClinVar aggregates 11 submissions: 7 classify as Uncertain significance, 1 as Likely benign, and 3 as not provided or not classified. No expert panel has issued a classification. Details ▾Hide ▴
Evidence considered
- ClinVar consensus: Uncertain significance (7 submitters)
- Likely benign (1 submitter).
- No expert panel classification available.
Sources
BA1 The variant allele frequency is substantially below the BA1 threshold of 1%. gnomAD v2.1 reports AF=0.00512% and gnomAD v4.1 reports AF=0.00348%. The variant is absent from gnomAD-Canada. Details ▾Hide ▴
Evidence considered
- gnomAD v2.1 AF=0.00512% (well below 1% BA1 threshold).
- gnomAD v4.1 AF=0.00348% (well below 1% BA1 threshold).
Sources
BS1 The variant allele frequency is below the BS1 threshold of 0.3%. gnomAD v2.1 reports AF=0.00512% and gnomAD v4.1 reports AF=0.00348%. The highest subpopulation frequency (South Asian, AF=0.045%) also falls below 0.3%. Details ▾Hide ▴
Evidence considered
- gnomAD v2.1 AF=0.00512% (below 0.3% BS1 threshold).
- gnomAD v4.1 AF=0.00348% (below 0.3% BS1 threshold).
- Highest subpopulation: South Asian AF=0.04518% (v4.1).
Sources
BS2 No homozygous observations of NM_001048171.1:c.995C>T are reported in gnomAD (v2.1: 0 homozygotes; v4.1: 0 homozygotes) or any other population database. BS2 requires observation in a homozygous state in healthy adults without disease manifestation. Details ▾Hide ▴
Evidence considered
- gnomAD v2.1: 0 homozygotes among 273
- 222 alleles.
- gnomAD v4.1: 0 homozygotes among 1
- 609
- 824 alleles.
Sources
BS3 The only functional evidence identified (D'Agostino et al. 2009, PMID:19092703, unverified) reports reduced glycosylase activity for p.S332L, which would indicate a damaging rather than benign effect. BS3 requires well-established functional studies showing no damaging effect on protein function or splicing. Details ▾Hide ▴
Evidence considered
- Exploratory pass identified D'Agostino et al. 2009 reporting reduced (not normal) glycosylase activity for p.S332L.
- No study demonstrates normal or wild-type-level function for this variant.
BS4 No segregation data are available to demonstrate lack of cosegregation with disease. No published family has been identified in which unaffected family members carry NM_001048171.1:c.995C>T in trans with a pathogenic MUTYH variant without developing MUTYH-associated polyposis. Details ▾Hide ▴
Evidence considered
- No family study with non-segregation data available for this variant.
Still missing
- No family-based segregation analysis for this variant.
BP2 No evidence demonstrates that NM_001048171.1:c.995C>T occurs in cis with a known pathogenic MUTYH variant in an individual with disease. Phase information is not available from ClinVar or the literature. Details ▾Hide ▴
Evidence considered
- No cis-configuration data with a pathogenic MUTYH variant has been reported.
Still missing
- No phase information for co-occurring pathogenic variants in MUTYH.
BP6 No reputable source has classified this variant as benign. ClinVar submissions predominantly classify it as Uncertain significance (7 submitters), with one Likely benign classification (Ambry Genetics, single submitter, criteria provided). A single Likely benign call from one laboratory does not meet the threshold for BP6. Details ▾Hide ▴
Evidence considered
- ClinVar: 7 VUS classifications
- 1 Likely benign (Ambry)
- 3 not provided/unclassified.
- No expert panel benign classification.
Sources
PS5 No variant-specific functional study has established a damaging effect meeting PS5 criteria. The variant has not been classified as pathogenic by any expert panel or multiple submitters with concordant criteria. Details ▾Hide ▴
Evidence considered
- ClinVar: 7 submitters classify as Uncertain significance
- 1 as Likely benign
- 1 as not provided.
- No expert panel classification.
Sources
Not assessed · 4 · no assessment recorded
PS3 The exploratory evidence pass identified a reference (D'Agostino et al. 2009, PMID:19092703) reporting reduced glycosylase activity for p.S332L. However, this paper was not retrieved as full-text in the case directory and could not be verified for variant-specific evidence. PS3 requires well-established functional data that can be independently confirmed. Details ▾Hide ▴
Evidence considered
- Exploratory evidence pass referenced D'Agostino et al. 2009 (PMID:19092703) reporting reduced glycosylase activity for p.S332L.
- PMID:19092703 full-text was not available in the case directory for independent verification.
Still missing
- PMID:19092703 full-text retrieval needed to confirm variant-specific functional data.
- Orthogonal functional assays (e.g.
- complementation in human cells) not identified.
- MUTYH VCEP functional thresholds not defined in the available CSPEC rule set.
PM1 Ser332 lies within the MUTYH C-terminal domain (approximately residues 301-490), a region implicated in PCNA binding and protein interactions. However, the MUTYH VCEP (ClinGen InSiGHT v1.0.0) does not provide an explicit PM1 domain definition or mutational hot spot specification for generic adjudication. Without VCEP-defined critical domain boundaries, PM1 cannot be applied under current framework rules. Details ▾Hide ▴
Evidence considered
- Residue S332 maps to the MUTYH C-terminal domain
- reported to be important for PCNA binding (Luncsford et al. 2010
- PMID:20571228).
- MUTYH CSPEC rule set v1.0.0 is unstructured and does not define a PM1 hot spot domain.
Still missing
- No explicit PM1 domain definition or mutational hot spot specification in the available MUTYH VCEP materials.
Sources
PP4 No detailed phenotype or family history information specific to the proband was available in the case materials. PP4 requires that the patient's phenotype or family history is highly specific for the disease associated with the gene. Details ▾Hide ▴
Evidence considered
- No proband-level phenotype data provided in the case materials.
Still missing
- Proband phenotype and family history not available for assessment.
BP5 BP5 applies when a variant is found in a case with an alternate molecular basis for disease. No proband-level genetic workup showing an alternative cause (e.g., biallelic pathogenic APC variants in a polyposis case) was available in the case materials. Details ▾Hide ▴
Evidence considered
- No alternate molecular diagnosis data available for proband.
Still missing
- Proband genetic testing results and alternative diagnoses not available.
Not applicable · 6· recorded as not applicable Show reasons ▾Hide reasons ▴
PVS1 N/ANM_001048171.1:c.995C>T is a missense variant (p.Ser332Leu) and does not fall into a null-variant bucket (nonsense, frameshift, or canonical ±1,2 splice consensus). The ClinGen SVI PVS1 decision tree does not apply to this variant class. Details ▾Hide ▴
Evidence considered
- Variant is a missense substitution (C>T at c.995)
- predicted protein consequence p.S332L.
- ClinGen SVI PVS1 generic framework (PMC6185798) does not support application to missense variants with no predicted splicing abnormality.
Sources
pvs1_variant_assessmentpvs1_generic_framework ↗
PM3 N/ASkipped per instruction: PM3 assessment deferred; no verified trans observations with a pathogenic variant available in case materials. Details ▾Hide ▴
No further detail was recorded.
PM4 N/ASkipped per instruction: PM4 applies to protein-length changing variants (in-frame indels, stop-loss); this variant is a single-nucleotide substitution. Details ▾Hide ▴
No further detail was recorded.
BP1 N/AMUTYH-associated polyposis can be caused by both truncating and missense variants. BP1 applies only when a gene's disease mechanism is exclusively through protein truncation. Details ▾Hide ▴
Evidence considered
- MUTYH pathogenic variants include both missense and truncating changes
- the gene does not have a truncation-only disease mechanism.
BP3 N/ASkipped per instruction: BP3 applies to in-frame insertions/deletions; this variant is a single-nucleotide substitution. Details ▾Hide ▴
No further detail was recorded.
BP7 N/ANM_001048171.1:c.995C>T is a missense variant (p.Ser332Leu), not a synonymous or intronic variant. BP7 applies only to synonymous variants for which splicing prediction algorithms predict no impact on the splice consensus sequence. Details ▾Hide ▴
Evidence considered
- c.995C>T is a missense substitution
- not a synonymous variant.
Identifiers
- Gene
- MUTYH
- Transcript
- NM_001048171.1
- Coding (HGVS c.)
- NM_001048171.1:c.995C>T
- Protein (HGVS p.)
- NP_001041636.1:p.(Ser332Leu)
- GRCh38
- chr1:45331810 G>A
- GRCh37
- chr1:45797482 G>A
- ClinVar
- 2867836, 1436543, 406827, 134862
Gene diagram
Every interpreted variant in MUTYH, mapped onto the exon structure of NM_001048171.1. Select a row to find it on the plot.
MUTYHNM_001048171.1
Fetching transcript structure from UCSC…
Exons
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Transcript span
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Strand
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Variants mapped
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Source
UCSC ncbiRefSeqCurated
All variants in MUTYH
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Select a row to find it on the plot; use the link to open its page.
| Protein | Location | Classification | Link |
|---|
gnomAD v4.1
56 / 1,609,824 alleles
AF 3.48e-05 · 0 homozygotes · FAF 0.000342
gnomAD v2.1
14 / 273,222 alleles
AF 5.12e-05 · 0 homozygotes · FAF 0.000204
gnomAD-Canada v1.0
0 / 0 alleles
AF 0 · 0 homozygotes · FAF 0
By genetic ancestry
gnomAD v4.1
AF 3.5e-05 · 56 / 1,609,824 alleles · 0 hom · FAF 0.00034
| South Asian41 / 90,744 | 0.00045 |
| East Asian3 / 44,724 | 6.7e-05 |
| Admixed American1 / 59,414 | 1.7e-05 |
| European (non-Finnish)11 / 1,177,952 | 9.3e-06 |
0 alternate alleles recorded in 6 other groups: Remaining individuals, European (Finnish), Amish, Middle Eastern, Ashkenazi Jewish, African/African American.
gnomAD v2.1
AF 5.1e-05 · 14 / 273,222 alleles · 0 hom · FAF 0.0002
| South Asian11 / 30,074 | 0.00037 |
| East Asian2 / 19,416 | 0.0001 |
| Admixed American1 / 34,558 | 2.9e-05 |
0 alternate alleles recorded in 5 other groups: African/African American, Ashkenazi Jewish, European (Finnish), European (non-Finnish), Remaining individuals.
gnomAD-Canada
AF 0 · 0 / 0 alleles · 0 hom
Statements
gnomAD v4.1
This variant is present in gnomAD v4.1 (AF= 3.47864e-05; MAF= 0.00348%, 56/1609824 alleles, homozygotes = 0) and has highest observed frequency in the South Asian population (AF= 0.000451821; MAF= 0.04518%, 41/90744 alleles, homozygotes = 0); grpmax FAF= 0.00034176.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 5.12404e-05; MAF= 0.00512%, 14/273222 alleles, homozygotes = 0) and has highest observed frequency in the South Asian population (AF= 0.000365764; MAF= 0.03658%, 11/30074 alleles, homozygotes = 0); grpmax FAF= 0.00020417.
SpliceAI and Pangolin
Other predictors
- REVEL
- 0.116
- BayesDel
- -0.476
How the predictions were used
BP4 SupportingMultiple lines of computational evidence suggest that this missense variant has no impact on gene product function. The REVEL score is 0.116 (below 0.5), BayesDel score is -0.476 (predicting benign), and SpliceAI predicts no splicing alteration (max delta = 0.00). All three in silico tools concordantly predict a benign effect. Details ▾Hide ▴
Evidence considered
- REVEL: 0.116 (benign
- below 0.5 threshold).
- BayesDel: -0.475899 (negative score
- consistent with benign).
- SpliceAI: max delta score 0.00 (no splicing impact).
- All three prediction tools concordantly indicate a benign effect.
Sources
PP3 Multiple in silico prediction tools suggest a benign impact of this missense change. REVEL score is 0.116 (below the 0.5 threshold), BayesDel score is -0.476 (negative, predicting benign), and SpliceAI predicts no splicing impact (max delta score = 0.00). No computational tool supports a deleterious effect, so PP3 is not met. Details ▾Hide ▴
Evidence considered
- REVEL: 0.116 (below 0.5 damaging threshold).
- BayesDel: -0.475899 (negative score
- predicts benign).
- SpliceAI: max delta 0.00 (no splicing impact predicted).
Sources
BP7 N/ANM_001048171.1:c.995C>T is a missense variant (p.Ser332Leu), not a synonymous or intronic variant. BP7 applies only to synonymous variants for which splicing prediction algorithms predict no impact on the splice consensus sequence. Details ▾Hide ▴
Evidence considered
- c.995C>T is a missense substitution
- not a synonymous variant.
Statement
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00). REVEL score = 0.116. BayesDel score = -0.475899.
9 paper records listed. No publication is explicitly linked to an applied criterion in the recorded metadata. None of the listed paper records explicitly indicates that the variant is named.
Recorded publications
-
PMID 21325953 ↗Lynch syndrome and MYH-associated polyposis: review and testing strategy.Goodenberger M et al. · 2011No paper-specific finding is recorded.
-
PMID 25645574 ↗ACG clinical guideline: Genetic testing and management of hereditary gastrointestinal cancer syndromes.No paper-specific finding is recorded.
-
PMID 25741868 ↗Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.No paper-specific finding is recorded.
-
PMID 26467025 ↗A Standardized DNA Variant Scoring System for Pathogenicity Assessments in Mendelian Disorders.No paper-specific finding is recorded.
-
PMID 23035301 ↗MUTYH Polyposis.Adam MP et al. · 1993No paper-specific finding is recorded.
-
PMID 23788249 ↗ACMG recommendations for reporting of incidental findings in clinical exome and genome sequencing.Green RC et al. · 2013No paper-specific finding is recorded.
-
PMID 24310308 ↗ACMG technical standards and guidelines for genetic testing for inherited colorectal cancer (Lynch syndrome, familial adenomatous polyposis, and MYH-associated polyposis).No paper-specific finding is recorded.
-
PMID 24728327 ↗Germline variation in cancer-susceptibility genes in a healthy, ancestrally diverse cohort: implications for individual genome sequencing.Bodian DL et al. · 2014No paper-specific finding is recorded.
-
PMID 28492532 ↗Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.No paper-specific finding is recorded.
Screenshots represent source records captured during evidence collection. Select one to view the recorded source content.
gnomAD v4.1
56 / 1,609,824 recorded alleles
Open source ↗
gnomAD v2.1
Captured gnomAD v2.1 source record
Open source ↗
SpliceAI Lookup
Recorded maximum delta 0.000
Open source ↗
ClinVar
7 Uncertain significance · 1 Likely benign · 1 Uncertain Significance
Open source ↗
COSMIC
Captured COSMIC source record
Open source ↗
Cancer hotspots
Captured Cancer Hotspots source record
Open source ↗
OncoKB
Captured OncoKB source record
Open source ↗
ClinGen CSpec
Captured ClinGen CSpec source record
Open source ↗
All source links
- ClinGen CSpec ↗cspec.genome.network/cspec/ui/svi/doc/1742141534
- ClinVar ↗www.ncbi.nlm.nih.gov/clinvar/variation/134862/
- gnomAD v2.1 ↗gnomad.broadinstitute.org/variant/1-45797482-G-A?dataset=gnomad_r2_1
- gnomAD v4.1 ↗gnomad.broadinstitute.org/variant/chr1-45331810-G-A?dataset=gnomad_r4
- SpliceAI Lookup ↗spliceailookup.broadinstitute.org/#variant=NM_001048171.1%3Ac.9…
- OncoKB ↗www.oncokb.org/gene/MUTYH/S332L
- COSMIC ↗cancer.sanger.ac.uk/cosmic/search?q=MUTYH+c.995C%3ET
- Cancer hotspots ↗www.cancerhotspots.org/
Statements for reports
The evidence statements recorded by the interpretation pipeline. They have not been reinterpreted by the page.
gnomAD v4.1
This variant is present in gnomAD v4.1 (AF= 3.47864e-05; MAF= 0.00348%, 56/1609824 alleles, homozygotes = 0) and has highest observed frequency in the South Asian population (AF= 0.000451821; MAF= 0.04518%, 41/90744 alleles, homozygotes = 0); grpmax FAF= 0.00034176.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 5.12404e-05; MAF= 0.00512%, 14/273222 alleles, homozygotes = 0) and has highest observed frequency in the South Asian population (AF= 0.000365764; MAF= 0.03658%, 11/30074 alleles, homozygotes = 0); grpmax FAF= 0.00020417.
ClinVar
Error retrieving ClinVar entry.
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00). REVEL score = 0.116. BayesDel score = -0.475899.
Functional
OncoKB did not identify variant-specific reviewed functional evidence for this variant; gene-level curated context is available for reviewer follow-up. MUTYH, a DNA glycosylase, is frequently mutated in colorectal cancer.
Somatic
This variant does not lie in a statistically significant hotspot. This variant has not previously been reported in somatic cancers (COSMIC).
Cancer Hotspots
This variant does not lie in a statistically significant hotspot.