About MET
No gene-level summary was recorded for this case.
Previous versions
Variant interpretation report
MET c.110T>C, p.(Val37Ala)
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.
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 Not recorded. 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: 2
Pathogenic criteria applied · 0
No pathogenic criterion marked as applied in the recorded assessment.
Benign criteria applied · 2
BS1Strong
BS1 · strong
Population frequency is above the 0.3% BS1 threshold. The highest observed frequency is 0.70588% in gnomAD v2.1 South Asian individuals and 0.68732% in gnomAD v4.1 South Asian individuals, which argues against a rare pathogenic germline variant.
BP4Supporting
BP4 · supporting
Multiple computational results support no damaging effect. SpliceAI predicts no significant splice impact with a maximum delta score of 0.00, REVEL is 0.142, and BayesDel is -0.247812, which together support a benign computational interpretation.
Recorded classification: Likely benign
gene-specific framework lacked a usable explicit final combination framework, so generic ACMG/AMP 2015 final-combination rules were applied as fallback; applied criteria: BS1 strong, BP4 supporting; combination = 1 strong benign + 1 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
879 / 1,613,956 alleles
gnomAD v4.1: 879 / 1,613,956 alleles. Recorded AF 0.000544625. Recorded homozygote count 10.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 0.000908223; MAF= 0.09082%, 255/280768 alleles, homozygotes = 1) and has highest observed frequency in the South Asian population (AF= 0.00705882; MAF= 0.70588%, 216/30600 alleles, homozygotes = 1); grpmax FAF= 0.0062877.
No screenshot for this evidence
Computational predictions
Not recorded
No SpliceAI or REVEL score is recorded in the fields used for this tile.
ClinVar submissions
Not recorded
A ClinVar laboratory submission summary was not recorded.
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. MET, a receptor tyrosine kinase, is recurrently altered by mutation or amplification in various cancer types.
No listed criterion applied
OncoKB ↗
COSMIC
Cancer Hotspots
Somatic evidence
Not assessed
No COSMIC evidence statement is recorded in this case.
Cancer Hotspots
This variant does not lie in a statistically significant hotspot.
Context only
For specialists
Technical detail
ACMG/AMP criteria under Not recorded, with the data and sources behind each one.
28 criteria with recorded statuses: 2 met · 5 not met · 12 not assessed · 9 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.
Met
Not met
Not assessed
Not applicable
The MET c.110T>C (p.Val37Ala) variant has been reported in ClinVar with likely benign and benign submissions.
This variant is present in population databases at a frequency above the BS1 threshold, with the highest observed frequency of 0.70588% in South Asian individuals in gnomAD v2.1 and 0.68732% in South Asian individuals in gnomAD v4.1, arguing against a rare pathogenic germline variant.
No well-established variant-specific functional study was identified to support either a damaging or a normal effect.
Computational evidence supports a benign interpretation, with SpliceAI predicting no significant splice impact (maximum delta score 0.00), REVEL of 0.142, and BayesDel of -0.247812.
No criteria match.
Met · 2
BS1 StrongPopulation frequency is above the 0.3% BS1 threshold. The highest observed frequency is 0.70588% in gnomAD v2.1 South Asian individuals and 0.68732% in gnomAD v4.1 South Asian individuals, which argues against a rare pathogenic germline variant. Details ▾Hide ▴
Rule
generic_acmg_bs1_af_gt_0.3pct
Evidence considered
- gnomAD v2.1 South Asian AF 0.00705882 (216/30600)
- 1 homozygote.
- gnomAD v4.1 South Asian AF 0.00687323 (626/91078)
- 10 homozygotes.
Sources
BP4 SupportingMultiple computational results support no damaging effect. SpliceAI predicts no significant splice impact with a maximum delta score of 0.00, REVEL is 0.142, and BayesDel is -0.247812, which together support a benign computational interpretation. Details ▾Hide ▴
Rule
generic_acmg_bp4
Evidence considered
- SpliceAI max delta score 0.00.
- REVEL score 0.142.
- BayesDel score -0.247812.
Sources
Not met · 5 · evaluated, threshold not reached
PS4 Available evidence does not show enrichment of this variant in affected individuals compared with population databases. The variant is present in ClinVar, but no case-control or multiple affected-case data supporting significant excess were identified. Details ▾Hide ▴
Rule
generic_acmg_ps4
Evidence considered
- ClinVar contains benign and likely benign submissions rather than affected-case enrichment evidence.
- Population frequency is readily detectable in gnomAD v2.1 and v4.1.
Still missing
- No case-control data were identified.
- No affected-individual count sufficient for PS4 was identified.
Sources
PM1 This variant is not supported to lie in a well-established mutational hotspot or critical functional domain without benign variation. Cancer Hotspots did not identify a statistically significant hotspot at codon 37. Details ▾Hide ▴
Rule
generic_acmg_pm1
Evidence considered
- Cancer Hotspots review found no significant hotspot row for MET V37.
- No variant-specific reviewed functional context was identified.
Still missing
- No domain-specific evidence showing codon 37 is a benign-variant-depleted hotspot was identified.
Sources
PM2 Population frequency is not low enough for PM2. In gnomAD v2.1 the highest subpopulation frequency is 0.70588% in South Asian individuals, and in gnomAD v4.1 the highest subpopulation frequency is 0.68732% in South Asian individuals, both above the 0.1% PM2 threshold. Details ▾Hide ▴
Rule
generic_acmg_pm2_af_lt_0.1pct
Evidence considered
- gnomAD v2.1 South Asian AF 0.00705882 (216/30600).
- gnomAD v4.1 South Asian AF 0.00687323 (626/91078).
Sources
PP3 Available computational evidence does not support a deleterious effect. SpliceAI predicts no significant splice impact with a maximum delta score of 0.00, REVEL is 0.142, and BayesDel is -0.247812. Details ▾Hide ▴
Rule
generic_acmg_pp3
Evidence considered
- SpliceAI max delta score 0.00.
- REVEL score 0.142.
- BayesDel score -0.247812.
Sources
BA1 Population frequency does not reach the 1% BA1 threshold. The highest observed subpopulation frequency is 0.70588% in gnomAD v2.1 South Asian and 0.68732% in gnomAD v4.1 South Asian. Details ▾Hide ▴
Rule
generic_acmg_ba1_af_gt_1pct
Evidence considered
- gnomAD v2.1 South Asian AF 0.00705882.
- gnomAD v4.1 South Asian AF 0.00687323.
Sources
Not assessed · 12 · no assessment recorded
PS1 No reviewed evidence was identified showing that a different nucleotide change produces the same amino acid substitution with an established pathogenic classification. Details ▾Hide ▴
Rule
generic_acmg_ps1
Evidence considered
- ClinVar record was reviewed for the exact variant only.
Still missing
- No same-amino-acid pathogenic comparator review was identified.
Sources
PS2 No confirmed de novo occurrence with verified parentage was identified for this variant. Details ▾Hide ▴
Rule
generic_acmg_ps2
Evidence considered
- No de novo evidence was identified in the reviewed materials.
Still missing
- No trio-based report or submitter note documenting confirmed de novo status was identified.
PS3 No well-established functional study demonstrating a damaging effect of this specific variant was identified. Details ▾Hide ▴
Rule
generic_acmg_ps3
Evidence considered
- Curated review did not identify variant-specific reviewed functional evidence.
Still missing
- No variant-specific validated functional assay was identified.
Sources
PM6 No presumed de novo occurrence without confirmed parentage was identified for this variant. Details ▾Hide ▴
Rule
generic_acmg_pm6
Evidence considered
- No de novo or presumed de novo evidence was identified.
Still missing
- No report describing a presumed de novo occurrence was identified.
PP1 No segregation data were identified for this variant. Details ▾Hide ▴
Rule
generic_acmg_pp1
Evidence considered
- No family segregation evidence was identified.
Still missing
- No pedigree or meiosis count supporting cosegregation was identified.
PP2 Available evidence does not establish that this gene has a low rate of benign missense variation and that missense variation is the predominant mechanism required for PP2 application in this case. Details ▾Hide ▴
Rule
generic_acmg_pp2
Evidence considered
- No reviewed PP2-supporting gene-level framework was identified.
Still missing
- No gene-specific missense-constraint framework for PP2 was identified.
PP4 No phenotype-specific evidence was provided to show that the clinical presentation is highly specific for a disorder caused by this gene. Details ▾Hide ▴
Rule
generic_acmg_pp4
Evidence considered
- Phenotype-specific case information was not available.
Still missing
- No detailed phenotype or testing-indication data were available for PP4 review.
BS2 Although this variant is observed in population databases, the available evidence was not sufficient to apply BS2 on the basis of observation in unaffected individuals alone. Details ▾Hide ▴
Rule
generic_acmg_bs2
Evidence considered
- gnomAD includes 1 homozygote in v2.1 and 10 homozygotes in v4.1.
Still missing
- No criterion-specific healthy adult or penetrance framework was identified for BS2.
Sources
BS3 No well-established functional study demonstrating normal function of this specific variant was identified. Details ▾Hide ▴
Rule
generic_acmg_bs3
Evidence considered
- Curated review did not identify variant-specific reviewed functional evidence.
Still missing
- No validated benign functional assay for this variant was identified.
Sources
BS4 No family data were identified showing lack of segregation of this variant with disease. Details ▾Hide ▴
Rule
generic_acmg_bs4
Evidence considered
- No pedigree data were identified.
Still missing
- No non-segregation data were identified.
BP2 No phase information was identified to show this variant occurring in trans with a pathogenic variant or in cis with another variant in a way that supports BP2. Details ▾Hide ▴
Rule
generic_acmg_bp2
Evidence considered
- No co-occurrence evidence was identified.
Still missing
- No phase or co-occurrence data were identified.
BP5 No alternate molecular diagnosis or other established cause of disease was provided that would support BP5. Details ▾Hide ▴
Rule
generic_acmg_bp5
Evidence considered
- No alternate diagnosis data were available.
Still missing
- No phenotype-level alternate diagnosis information was available.
Not applicable · 9· recorded as not applicable Show reasons ▾Hide reasons ▴
PVS1 N/AThis variant is a missense substitution, p.(Val37Ala), and does not fall into the generic PVS1 null-variant categories of nonsense, frameshift, or canonical +/-1 or 2 splice variants. Details ▾Hide ▴
Rule
generic_acmg_pvs1_null_variant_framework
Evidence considered
- Variant consequence is missense p.(Val37Ala).
- Generic PVS1 scaffold did not place this variant in an eligible null-variant bucket.
Sources
pvs1_variant_assessmentpvs1_generic_framework ↗
PM3 N/ANo evidence relevant to trans occurrence in a recessive disease context was identified for this variant. Details ▾Hide ▴
Rule
generic_acmg_pm3
Evidence considered
- No trans observations were identified.
PM4 N/AThis variant is a missense substitution and does not change protein length or create an in-frame insertion or deletion. Details ▾Hide ▴
Rule
generic_acmg_pm4
Evidence considered
- Protein consequence is p.(Val37Ala).
PM5 N/AClassic same-residue PM5 comparator logic could not be confirmed for this case, and no reviewed pathogenic same-residue comparator variant was identified. Details ▾Hide ▴
Rule
generic_acmg_pm5
Evidence considered
- PM5 candidate review did not confirm safe use of classic same-residue PM5 semantics.
Still missing
- No validated same-residue pathogenic comparator was identified.
Sources
pm5_candidates
PP5 N/AThis criterion was not used because external assertions without primary supporting evidence are not applied here. Details ▾Hide ▴
Rule
generic_acmg_pp5
Evidence considered
- ClinVar assertions were reviewed directly rather than used as PP5 evidence.
Sources
BP1 N/ABP1 was not applied because the required pattern of disease being caused primarily by truncating variants was not established for this case. Details ▾Hide ▴
Rule
generic_acmg_bp1
Evidence considered
- No BP1-supporting gene-level mechanism review was identified.
BP3 N/AThis variant is not an in-frame insertion or deletion in a repetitive region. Details ▾Hide ▴
Rule
generic_acmg_bp3
Evidence considered
- Variant type is missense substitution.
BP6 N/AThis criterion was not used because external assertions without accessible supporting evidence are not applied here. Details ▾Hide ▴
Rule
generic_acmg_bp6
Evidence considered
- ClinVar assertions were reviewed directly rather than used as BP6 evidence.
Sources
BP7 N/AThis variant is not a synonymous or deep intronic change, so BP7 does not apply. Details ▾Hide ▴
Rule
generic_acmg_bp7
Evidence considered
- Variant consequence is missense p.(Val37Ala).
Identifiers
- Gene
- MET
- Transcript
- NM_001127500.3
- Coding (HGVS c.)
- NM_001127500.3:c.110T>C
- Protein (HGVS p.)
- NP_001120972.1:p.(Val37Ala)
- GRCh38
- chr7:116699194 T>C
- GRCh37
- chr7:116339248 T>C
Gene diagram
Every interpreted variant in MET, mapped onto the exon structure of NM_001127500.3. Select a row to find it on the plot.
METNM_001127500.3
Fetching transcript structure from UCSC…
Exons
—
Transcript span
—
Strand
—
Variants mapped
—
Source
UCSC ncbiRefSeqCurated
All variants in MET
—
Select a row to find it on the plot; use the link to open its page.
| Protein | Location | Classification | Link |
|---|
gnomAD v4.1
879 / 1,613,956 alleles
AF 0.000545 · 10 homozygotes · FAF 0.00643
gnomAD v2.1
255 / 280,768 alleles
AF 0.000908 · 1 homozygotes · FAF 0.00629
By genetic ancestry
gnomAD v4.1
AF 0.00054 · 879 / 1,613,956 alleles · 10 hom · FAF 0.0064
| South Asian626 / 91,078 | 0.006910 hom |
| Middle Eastern9 / 6,060 | 0.0015 |
| Ashkenazi Jewish36 / 29,600 | 0.0012 |
| Remaining individuals46 / 62,496 | 0.00074 |
| European (non-Finnish)157 / 1,179,916 | 0.00013 |
| Admixed American3 / 59,978 | 5e-05 |
| African/African American2 / 75,022 | 2.7e-05 |
0 alternate alleles recorded in 3 other groups: European (Finnish), Amish, East Asian.
gnomAD v2.1
AF 0.00091 · 255 / 280,768 alleles · 1 hom · FAF 0.0063
| South Asian216 / 30,600 | 0.00711 hom |
| Ashkenazi Jewish11 / 10,358 | 0.0011 |
| Remaining individuals4 / 7,146 | 0.00056 |
| European (non-Finnish)23 / 128,602 | 0.00018 |
| African/African American1 / 24,190 | 4.1e-05 |
0 alternate alleles recorded in 3 other groups: Admixed American, East Asian, European (Finnish).
Statements
gnomAD v4.1
This variant is present in gnomAD v4.1 (AF= 0.000544625; MAF= 0.05446%, 879/1613956 alleles, homozygotes = 10) and has highest observed frequency in the South Asian population (AF= 0.00687323; MAF= 0.68732%, 626/91078 alleles, homozygotes = 10); grpmax FAF= 0.00642681.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 0.000908223; MAF= 0.09082%, 255/280768 alleles, homozygotes = 1) and has highest observed frequency in the South Asian population (AF= 0.00705882; MAF= 0.70588%, 216/30600 alleles, homozygotes = 1); grpmax FAF= 0.0062877.
Other predictors
- REVEL
- Not available
- BayesDel
- Not available
How the predictions were used
BP4 SupportingMultiple computational results support no damaging effect. SpliceAI predicts no significant splice impact with a maximum delta score of 0.00, REVEL is 0.142, and BayesDel is -0.247812, which together support a benign computational interpretation. Details ▾Hide ▴
Rule
generic_acmg_bp4
Evidence considered
- SpliceAI max delta score 0.00.
- REVEL score 0.142.
- BayesDel score -0.247812.
Sources
PP3 Available computational evidence does not support a deleterious effect. SpliceAI predicts no significant splice impact with a maximum delta score of 0.00, REVEL is 0.142, and BayesDel is -0.247812. Details ▾Hide ▴
Rule
generic_acmg_pp3
Evidence considered
- SpliceAI max delta score 0.00.
- REVEL score 0.142.
- BayesDel score -0.247812.
Sources
BP7 N/AThis variant is not a synonymous or deep intronic change, so BP7 does not apply. Details ▾Hide ▴
Rule
generic_acmg_bp7
Evidence considered
- Variant consequence is missense p.(Val37Ala).
Statement
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00). REVEL score = 0.142. BayesDel score = -0.247812.
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
879 / 1,613,956 recorded alleles
Open source ↗
gnomAD v2.1
Captured gnomAD v2.1 source record
Open source ↗
SpliceAI Lookup
Captured SpliceAI source record
Open source ↗
ClinVar
Captured ClinVar source record
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 ↗
All source links
- ClinVar ↗www.ncbi.nlm.nih.gov/clinvar/variation/41610/
- gnomAD v2.1 ↗gnomad.broadinstitute.org/variant/7-116339248-T-C?dataset=gnomad_r2_1
- gnomAD v4.1 ↗gnomad.broadinstitute.org/variant/chr7-116699194-T-C?dataset=gn…
- SpliceAI Lookup ↗spliceailookup.broadinstitute.org/#variant=NM_001127500.3%3Ac.1…
- OncoKB ↗www.oncokb.org/gene/MET/V37A
- COSMIC ↗cancer.sanger.ac.uk/cosmic/mutation/overview?id=108585215
- 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= 0.000544625; MAF= 0.05446%, 879/1613956 alleles, homozygotes = 10) and has highest observed frequency in the South Asian population (AF= 0.00687323; MAF= 0.68732%, 626/91078 alleles, homozygotes = 10); grpmax FAF= 0.00642681.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 0.000908223; MAF= 0.09082%, 255/280768 alleles, homozygotes = 1) and has highest observed frequency in the South Asian population (AF= 0.00705882; MAF= 0.70588%, 216/30600 alleles, homozygotes = 1); grpmax FAF= 0.0062877.
ClinVar
This variant has been reported in ClinVar as Likely benign (6 clinical laboratories) and as Benign (3 clinical laboratories). (ClinVarID = 41610)
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00). REVEL score = 0.142. BayesDel score = -0.247812.
Functional
OncoKB did not identify variant-specific reviewed functional evidence for this variant; gene-level curated context is available for reviewer follow-up. MET, a receptor tyrosine kinase, is recurrently altered by mutation or amplification in various cancer types.
Somatic
This variant does not lie in a statistically significant hotspot. This variant has previously been reported in somatic cancers (COSMIC; COSV104627100, n = 1 times).
Cancer Hotspots
This variant does not lie in a statistically significant hotspot.