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MUTYHc.690+12G>TLikely benign
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Variant interpretation report

MUTYH c.690+12G>T, p.?

NM_001128425.2:c.690+12G>T NP_001121897.1:p.? View identifiers
Classification
Likely benign

Variant description:

No variant summary was recorded for this case.

Five-step scale from benign to pathogenic. This variant is likely benign. Select a step to read what it means.

Likely benign.A likely benign classification under the recorded framework.

In plain language

Gene-level background from the recorded interpretation.

About MUTYH

No gene-level summary was recorded for this case.

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: 0 Benign evidence criteria: 3
Pathogenic criteria applied · 0

No pathogenic criterion marked as applied in the recorded assessment.

Benign criteria applied · 3
BP4Supporting
BP4 · supporting

Multiple lines of computational evidence suggest no impact on gene product or splicing. SpliceAI predicts no significant splice alteration (max delta score = 0.00). REVEL and BayesDel could not be assessed for this intronic variant, but the available evidence uniformly indicates a benign computational profile.

BP6Supporting
BP6 · supporting

This variant is classified as Likely benign in ClinVar by GeneDx (VariationID: 386695), a clinical diagnostic laboratory. The classification is supported by in silico evidence indicating a conservative change at a poorly conserved position. While a single submitter, GeneDx is a reputable clinical laboratory whose classification constitutes supporting evidence for a benign interpretation.

BP7Supporting
BP7 · supporting

NM_001128425.2:c.690+12G>T is an intronic variant at position +12, outside the conserved splice consensus region. SpliceAI predicts no impact on splicing (max delta score = 0.00), with no predicted donor/acceptor gain or loss. This is consistent with a silent intronic change with no predicted functional consequence on splicing.

Recorded classification: Likely benign

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: BP4 supporting, BP6 supporting, BP7 supporting; combination = 3 supporting benign, which maps to Likely Benign.

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
Not recorded

gnomAD v4.1 allele counts were not recorded for this variant.

gnomAD v2.1

Absent from gnomAD v2.1.

gnomAD-Canada

Absent from gnomAD-Canada v1.0.

No listed criterion applied
gnomAD v4.1 ↗gnomAD v2.1 ↗gnomAD-Canada ↗
SpliceAI score
0.000 maximum delta

Recorded SpliceAI maximum delta score: 0.000. Refer to the recorded PP3/BP4 rationale for interpretation.

Applied · BP4, BP7 → SpliceAI ↗
ClinVar submissions
1 reported laboratory submissions

1 Likely benign. ClinVar API review status: criteria provided, single submitter.

Applied · BP6 → ClinVar ↗
No screenshot for this evidence
Functional evidence
Not recorded

No standalone functional evidence summary is recorded in evidence_summary.functional.

No listed criterion applied OncoKB ↗
Somatic evidence
No matching record reported

This variant has not previously been reported in somatic cancers (COSMIC).

Context only COSMIC ↗
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: 3 met · 18 not met · 1 not assessed · 7 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.

Pathogenic
PVS1PS1PS2PS3PS4PM1PM2PM3PM4PM5PM6PP1PP2PP3PP4PP5PS5
Benign
BA1BS1BS2BS3BS4BP1BP2BP3BP4BP5BP6BP7
Met Not met Not assessed Not applicable

Multiple lines of computational evidence (SpliceAI max delta = 0.00) predict no splicing impact for this intronic variant at position +12 of intron 8, satisfying BP4 (supporting benign).

This intronic variant is outside the conserved splice consensus region, and splicing prediction algorithms uniformly predict no splice alteration, satisfying BP7 (supporting benign).

This variant has been reported in ClinVar as Likely benign by a single clinical laboratory (GeneDx, VariationID: 386695), satisfying BP6 (supporting benign).

Three supporting benign criteria (BP4, BP6, BP7) are met. Under generic ACMG/AMP 2015 classification rules, this is sufficient for a Likely benign classification (u22652 supporting benign criteria).

No pathogenic criteria are met. PVS1 is not met (intronic variant outside canonical splice consensus, no predicted splice effect). PS3 is not met (no functional data). PP3 is not met (SpliceAI predicts no effect). PM2 could not be reliably assessed due to uncertain gnomAD coverage of this intronic position.

Met · 3

BP4 SupportingMultiple lines of computational evidence suggest no impact on gene product or splicing. SpliceAI predicts no significant splice alteration (max delta score = 0.00). REVEL and BayesDel could not be assessed for this intronic variant, but the available evidence uniformly indicates a benign computational profile. Details ▾Hide ▴
Evidence considered
  • SpliceAI max delta = 0.00
  • no predicted donor/acceptor gain or loss
  • Pangolin splice scores: SG 0.09
  • SL -0.02 (negligible)
Sources
spliceai ↗
BP6 SupportingThis variant is classified as Likely benign in ClinVar by GeneDx (VariationID: 386695), a clinical diagnostic laboratory. The classification is supported by in silico evidence indicating a conservative change at a poorly conserved position. While a single submitter, GeneDx is a reputable clinical laboratory whose classification constitutes supporting evidence for a benign interpretation. Details ▾Hide ▴
Evidence considered
  • ClinVar: Likely benign
  • single submitter (GeneDx
  • SCV000528440)
  • ClinVar review status: criteria provided
  • single submitter
  • Submitter cited in silico evidence suggesting benign effect
Still missing
  • Single submitter only
  • no expert panel review
Sources
clinvar ↗
BP7 SupportingNM_001128425.2:c.690+12G>T is an intronic variant at position +12, outside the conserved splice consensus region. SpliceAI predicts no impact on splicing (max delta score = 0.00), with no predicted donor/acceptor gain or loss. This is consistent with a silent intronic change with no predicted functional consequence on splicing. Details ▾Hide ▴
Evidence considered
  • Intronic variant at +12 position
  • outside conserved splice donor consensus
  • SpliceAI max delta = 0.00
  • no predicted splicing alteration
  • No cryptic splice site creation or native splice site disruption predicted
Sources
spliceai ↗

Not met · 18 · evaluated, threshold not reached

PVS1 NM_001128425.2:c.690+12G>T is an intronic variant at position +12 of intron 8, outside the canonical splice consensus (u00b11,2). The variant does not fall into any generic PVS1 null-variant bucket (nonsense, frameshift, or canonical splice site). SpliceAI predicts no significant splice impact (max delta score = 0.00). PVS1 is not applicable for this variant class. Details ▾Hide ▴
Evidence considered
  • Intronic variant at +12 position
  • outside canonical splice consensus
  • SpliceAI max delta = 0.00
  • no predicted splicing impact
  • Variant does not meet criteria for PVS1 under ClinGen SVI PVS1 framework (PMC6185798)
Sources
spliceai ↗pvs1_generic_framework ↗
PS2 No de novo observation has been reported for NM_001128425.2:c.690+12G>T in the available evidence. No publications identified for this variant. Details ▾Hide ▴
Still missing
  • No de novo data available for this variant
PS3 No functional studies have been performed on NM_001128425.2:c.690+12G>T. No publications were identified for this variant. SpliceAI predicts no splicing impact (max delta = 0.00), which does not support a pathogenic functional effect. Details ▾Hide ▴
Still missing
  • No experimental functional data exists for this variant
Sources
spliceai ↗
PS4 No case-control studies or prevalence data comparing affected versus unaffected individuals are available for NM_001128425.2:c.690+12G>T. Details ▾Hide ▴
Still missing
  • No case-control or prevalence data available
PM1 This is an intronic variant at position +12 of intron 8, outside any critical or well-established functional domain. No splice-region hotspot or functionally characterized domain encompasses this position. Details ▾Hide ▴

No further detail was recorded.

PM6 No de novo observation has been reported for NM_001128425.2:c.690+12G>T in the available evidence. No publications identified for this variant. Details ▾Hide ▴
Still missing
  • No de novo data available
PP1 No cosegregation data are available for NM_001128425.2:c.690+12G>T in affected families. Details ▾Hide ▴
Still missing
  • No family segregation data available
PP3 Multiple lines of computational evidence do not support a deleterious effect. SpliceAI predicts no significant splice impact (max delta score = 0.00). REVEL and BayesDel are not available for this intronic variant. There is no in silico evidence supporting pathogenicity. Details ▾Hide ▴
Evidence considered
  • SpliceAI max delta = 0.00
  • no predicted splicing alteration
  • REVEL score not available (intronic variant)
  • BayesDel score not available (intronic variant)
Sources
spliceai ↗
PP4 No patient phenotype data are available for this variant. PP4 requires the variant to be identified in an individual with a phenotype highly specific for the gene/disease. Details ▾Hide ▴
Still missing
  • No phenotype data available for carriers of this variant
PP5 ClinVar classifies this variant as Likely benign (single submitter, GeneDx), not as pathogenic. There is no reputable source report of pathogenicity. Details ▾Hide ▴
Evidence considered
  • ClinVar classification: Likely benign (VariationID: 386695)
Sources
clinvar ↗
BA1 This variant is not observed at an allele frequency >1% in any population database. gnomAD data for this intronic position is inconclusive but does not demonstrate a frequency consistent with BA1. Details ▾Hide ▴
Evidence considered
  • No evidence of allele frequency >1% in any population database
Sources
gnomad_v2 ↗gnomad_v4 ↗
BS1 This variant is not observed at an allele frequency >0.3% in any population database. gnomAD data for this intronic position is inconclusive but does not demonstrate a frequency consistent with BS1. Details ▾Hide ▴
Evidence considered
  • No evidence of allele frequency >0.3% in any population database
Sources
gnomad_v2 ↗gnomad_v4 ↗
BS2 No data available for observation of this variant in healthy adult individuals. MUTYH-associated polyposis follows autosomal recessive inheritance, which limits the applicability of BS2 anyway. Details ▾Hide ▴
Still missing
  • No healthy control observation data available
BS3 No well-established functional studies have been performed on NM_001128425.2:c.690+12G>T that show no damaging effect. While SpliceAI predicts no splicing impact, this is computational evidence (BP4/BP7 territory) rather than well-established functional data. Details ▾Hide ▴
Still missing
  • No experimental functional studies available
Sources
spliceai ↗
BS4 No cosegregation data are available to demonstrate lack of segregation with disease for NM_001128425.2:c.690+12G>T. Details ▾Hide ▴
Still missing
  • No family segregation data available
BP2 BP2 requires observation in trans with a pathogenic variant in a fully penetrant dominant disorder. MUTYH-associated polyposis is an autosomal recessive disorder, and no trans data are available for this variant. Details ▾Hide ▴
Still missing
  • No trans-phase data available
  • MUTYH is autosomal recessive
BP5 No evidence that this variant has been observed in a case where an alternate molecular basis for disease was identified. Details ▾Hide ▴
Still missing
  • No alternate molecular basis data available
PS5 ClinVar classifies this variant as Likely benign (single submitter, GeneDx), not as pathogenic. There is no established reputable source reporting this variant as pathogenic. Details ▾Hide ▴
Evidence considered
  • ClinVar classification: Likely benign (VariationID: 386695)
Sources
clinvar ↗

Not assessed · 1 · no assessment recorded

PM2 gnomAD data for this intronic position could not be reliably assessed. gnomAD v2.1 (exomes only) does not cover intronic regions. gnomAD v4.1 and gnomAD-Canada returned null allele counts, indicating data extraction failure or incomplete coverage rather than confirmed absence. PM2 cannot be reliably applied without validated population frequency data for this intronic position. Details ▾Hide ▴
Evidence considered
  • gnomAD v2.1: ac null
  • an null — not covered (exomes only)
  • gnomAD v4.1: ac null
  • an null — extraction incomplete
  • gnomAD-Canada: ac 0
  • an 0 — zero coverage at this position
Still missing
  • Reliable population frequency data for this intronic position is unavailable
Sources
gnomad_v2 ↗gnomad_v4 ↗gnomad_canada ↗
Not applicable · 7· recorded as not applicable Show reasons ▾Hide reasons ▴
PS1 N/APS1 requires a different nucleotide change producing the same amino acid change as a known pathogenic variant. This is an intronic variant that does not alter the protein sequence. Details ▾Hide ▴

No further detail was recorded.

PM3 N/APM3 requires observation of the variant in trans with a pathogenic variant in a recessive disorder. This variant was not observed in trans with any pathogenic MUTYH variant in the available evidence, and no proband genotype data were provided. Details ▾Hide ▴

No further detail was recorded.

PM4 N/APM4 applies to protein length changes from in-frame deletions/insertions or stop-loss variants. This is a single nucleotide substitution in an intron, not a protein-length-altering variant. Details ▾Hide ▴

No further detail was recorded.

PM5 N/APM5 requires a different missense change at the same amino acid residue as a known pathogenic variant. This is an intronic variant that does not alter any amino acid residue. Details ▾Hide ▴

No further detail was recorded.

PP2 N/APP2 applies to missense variants in genes where missense variants are a common mechanism of disease and benign missense variation is rare. This is an intronic variant, not a missense change. Details ▾Hide ▴

No further detail was recorded.

BP1 N/ABP1 applies to missense variants in genes where a truncating mechanism is primarily known to cause disease. This is an intronic variant, not a missense change. Details ▾Hide ▴

No further detail was recorded.

BP3 N/ABP3 applies to in-frame deletions or insertions in repetitive regions. This is a single nucleotide substitution, not an in-frame indel. Details ▾Hide ▴

No further detail was recorded.

Identifiers

Gene
MUTYH
Transcript
NM_001128425.2
Coding (HGVS c.)
NM_001128425.2:c.690+12G>T
Protein (HGVS p.)
NP_001121897.1:p.?
GRCh38
chr1:45332562 C>A
GRCh37
chr1:45798234 C>A
ClinVar
386695

Gene diagram

Every interpreted variant in MUTYH, mapped onto the exon structure of NM_001128425.2. Select a row to find it on the plot.

MUTYHNM_001128425.2
Fetching transcript structure from UCSC…
gnomAD v4.1 Allele count data not recorded
gnomAD v2.1 Allele count data not recorded
gnomAD-Canada v1.0 Allele count data not recorded

Statements

gnomAD v4.1

Absent from gnomAD v4.1.

gnomAD v2.1

Absent from gnomAD v2.1.

gnomAD-Canada

Absent from gnomAD-Canada v1.0.

SpliceAI and Pangolin

Pangolin splice lossmagnitude shown
-0.020
Pangolin splice gain
0.090

Other predictors

REVEL
Not available
BayesDel
Not available

How the predictions were used

BP4 SupportingMultiple lines of computational evidence suggest no impact on gene product or splicing. SpliceAI predicts no significant splice alteration (max delta score = 0.00). REVEL and BayesDel could not be assessed for this intronic variant, but the available evidence uniformly indicates a benign computational profile. Details ▾Hide ▴
Evidence considered
  • SpliceAI max delta = 0.00
  • no predicted donor/acceptor gain or loss
  • Pangolin splice scores: SG 0.09
  • SL -0.02 (negligible)
Sources
spliceai ↗
BP7 SupportingNM_001128425.2:c.690+12G>T is an intronic variant at position +12, outside the conserved splice consensus region. SpliceAI predicts no impact on splicing (max delta score = 0.00), with no predicted donor/acceptor gain or loss. This is consistent with a silent intronic change with no predicted functional consequence on splicing. Details ▾Hide ▴
Evidence considered
  • Intronic variant at +12 position
  • outside conserved splice donor consensus
  • SpliceAI max delta = 0.00
  • no predicted splicing alteration
  • No cryptic splice site creation or native splice site disruption predicted
Sources
spliceai ↗
PP3 Multiple lines of computational evidence do not support a deleterious effect. SpliceAI predicts no significant splice impact (max delta score = 0.00). REVEL and BayesDel are not available for this intronic variant. There is no in silico evidence supporting pathogenicity. Details ▾Hide ▴
Evidence considered
  • SpliceAI max delta = 0.00
  • no predicted splicing alteration
  • REVEL score not available (intronic variant)
  • BayesDel score not available (intronic variant)
Sources
spliceai ↗

Statement

In silico

SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00).

0 paper records listed. No publication is explicitly linked to an applied criterion in the recorded metadata.

Screenshots represent source records captured during evidence collection. Select one to view the recorded source content.

gnomAD v4.1 Captured gnomAD v4.1 source record Open source ↗
gnomAD v2.1 Captured gnomAD v2.1 source record Open source ↗
SpliceAI Lookup Recorded maximum delta 0.000 Open source ↗
ClinVar 1 Likely benign Open source ↗
COSMIC Captured COSMIC source record Open source ↗
ClinGen CSpec Captured ClinGen CSpec source record Open source ↗

All source links

Statements for reports

The evidence statements recorded by the interpretation pipeline. They have not been reinterpreted by the page.

gnomAD v4.1

Absent from gnomAD v4.1.

gnomAD v2.1

Absent from gnomAD v2.1.

gnomAD-Canada

Absent from gnomAD-Canada v1.0.

ClinVar

This variant has been reported in ClinVar as Likely benign (1 clinical laboratory). (ClinVarID = 386695)

In silico

SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00).

Somatic

This variant has not previously been reported in somatic cancers (COSMIC).