7-116795989-G-T

Variant names:

• chr7-116795989-G-T
• NM_000245.4:c.4038G>T

Variant summary

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

The NM_000245.4(MET):​c.4038G>T​(p.Gly1346Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MET NM_000245.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.316

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.4038G>T	p.Gly1346Gly	synonymous_variant	Exon 21 of 21	ENST00000397752.8	NP_000236.2
MET	NM_001127500.3	c.4092G>T	p.Gly1364Gly	synonymous_variant	Exon 21 of 21		NP_001120972.1
MET	NM_001324402.2	c.2748G>T	p.Gly916Gly	synonymous_variant	Exon 20 of 20		NP_001311331.1
MET	XM_011516223.2	c.4095G>T	p.Gly1365Gly	synonymous_variant	Exon 22 of 22		XP_011514525.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MET	ENST00000397752.8	c.4038G>T	p.Gly1346Gly	synonymous_variant	Exon 21 of 21	1	NM_000245.4	ENSP00000380860.3
MET	ENST00000318493.11	c.4092G>T	p.Gly1364Gly	synonymous_variant	Exon 21 of 21	1		ENSP00000317272.6
MET	ENST00000436117.3	n.*1643G>T		non_coding_transcript_exon_variant	Exon 20 of 20	1		ENSP00000410980.2
MET	ENST00000436117.3	n.*1643G>T		3_prime_UTR_variant	Exon 20 of 20	1		ENSP00000410980.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 57

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	12
DANN	Benign	0.64

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.28		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.28		Position offset: -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: chr7-116436043;