7-116771920-C-G

Variant names:

• chr7-116771920-C-G
• NM_000245.4:c.2959C>G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_000245.4(MET):​c.2959C>G​(p.Arg987Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MET NM_000245.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.85

Genes affected

MET (HGNC:7029): (MET proto-oncogene, receptor tyrosine kinase) This gene encodes a member of the receptor tyrosine kinase family of proteins and the product of the proto-oncogene MET. The encoded preproprotein is proteolytically processed to generate alpha and beta subunits that are linked via disulfide bonds to form the mature receptor. Further processing of the beta subunit results in the formation of the M10 peptide, which has been shown to reduce lung fibrosis. Binding of its ligand, hepatocyte growth factor, induces dimerization and activation of the receptor, which plays a role in cellular survival, embryogenesis, and cellular migration and invasion. Mutations in this gene are associated with papillary renal cell carcinoma, hepatocellular carcinoma, and various head and neck cancers. Amplification and overexpression of this gene are also associated with multiple human cancers. [provided by RefSeq, May 2016]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MET	NM_000245.4	c.2959C>G	p.Arg987Gly	missense_variant	Exon 14 of 21	ENST00000397752.8	NP_000236.2
MET	NM_001127500.3	c.3013C>G	p.Arg1005Gly	missense_variant	Exon 14 of 21		NP_001120972.1
MET	NM_001324402.2	c.1669C>G	p.Arg557Gly	missense_variant	Exon 13 of 20		NP_001311331.1
MET	XM_011516223.2	c.3016C>G	p.Arg1006Gly	missense_variant	Exon 15 of 22		XP_011514525.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MET	ENST00000397752.8	c.2959C>G	p.Arg987Gly	missense_variant	Exon 14 of 21	1	NM_000245.4	ENSP00000380860.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 04, 2025

Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.79
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.030
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.41	T;.
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.94	D;D
M_CAP	Benign	0.073	D
MetaRNN	Uncertain	0.64	D;D
MetaSVM	Benign	-0.30	T
MutationAssessor	Uncertain	2.0	M;.
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-1.2	N;N
REVEL	Uncertain	0.44
Sift	Uncertain	0.0080	D;D
Sift4G	Uncertain	0.047	D;D
Polyphen		0.96	D;D
Vest4		0.81
MutPred		0.55		Loss of solvent accessibility (P = 0.0159);.;
MVP		0.76
MPC		1.0
ClinPred		0.96	D
GERP RS		4.7
Varity_R		0.41
gMVP		0.74

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-116411974; COSMIC: COSV59260012; COSMIC: COSV59260012;