chr7-116771932-C-T
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4BS1_Supporting
The NM_000245.4(MET):c.2971C>T(p.Pro991Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000013 in 1,461,624 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P991L) has been classified as Uncertain significance.
Frequency
Consequence
NM_000245.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MET | NM_000245.4 | c.2971C>T | p.Pro991Ser | missense_variant | 14/21 | ENST00000397752.8 | |
MET | NM_001127500.3 | c.3025C>T | p.Pro1009Ser | missense_variant | 14/21 | ||
MET | NM_001324402.2 | c.1681C>T | p.Pro561Ser | missense_variant | 13/20 | ||
MET | XM_011516223.2 | c.3028C>T | p.Pro1010Ser | missense_variant | 15/22 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MET | ENST00000397752.8 | c.2971C>T | p.Pro991Ser | missense_variant | 14/21 | 1 | NM_000245.4 | P3 | |
MET | ENST00000318493.11 | c.3025C>T | p.Pro1009Ser | missense_variant | 14/21 | 1 | A2 | ||
MET | ENST00000436117.3 | c.*576C>T | 3_prime_UTR_variant, NMD_transcript_variant | 13/20 | 1 | ||||
MET | ENST00000454623.1 | c.283+278C>T | intron_variant | 5 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.0000282 AC: 7AN: 248608Hom.: 0 AF XY: 0.0000371 AC XY: 5AN XY: 134830
GnomAD4 exome AF: 0.0000130 AC: 19AN: 1461624Hom.: 0 Cov.: 32 AF XY: 0.0000151 AC XY: 11AN XY: 727114
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Osteofibrous dysplasia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Baylor Genetics | May 25, 2021 | This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Apr 07, 2021 | In silico analysis supports that this missense variant does not alter protein structure/function; Published functional studies demonstrate a damaging effect: increased and persistent tyrosine phosphorylation, colony formation in soft agar, and tumorgeneis in athymic mice (Lee 2000); This variant is associated with the following publications: (PMID: 11042681) - |
Papillary renal cell carcinoma type 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. - |
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 14, 2022 | The p.P1009S variant (also known as c.3025C>T), located in coding exon 13 of the MET gene, results from a C to T substitution at nucleotide position 3025. The proline at codon 1009 is replaced by serine, an amino acid with similar properties. This alteration has been reported in a patient with primary gastric cancer (Lee JH et al. Oncogene, 2000 Oct;19:4947-53). Lee et al. (2000) also examined the impact of this alteration in when expressed in a mouse embryonic fibroblast cell line and found it results in increased tyrosine phosphorylation compared to wild-type, as well as highly tumorigenic colony formation in soft agar, leading authors to conclude that it could contribute to tumorigenesis of gastric cancer. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Renal cell carcinoma Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 25, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at