rs555099334

Variant names:

• chr7-116795771-C-A
• NM_000245.4:c.3915C>A

Your query was ambiguous. Multiple possible variants found:

• chr7-116795771-C-A
• chr7-116795771-C-G
• chr7-116795771-C-T

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_000245.4(MET):​c.3915C>A​(p.Pro1305Pro) 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. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MET NM_000245.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.46

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 Likely_benign. Variant got -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP6: Variant 7-116795771-C-A is Benign according to our data. Variant chr7-116795771-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 1736580.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-3.46 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MET	NM_000245.4	c.3915C>A	p.Pro1305Pro	synonymous_variant	Exon 20 of 21	ENST00000397752.8	NP_000236.2
MET	NM_001127500.3	c.3969C>A	p.Pro1323Pro	synonymous_variant	Exon 20 of 21		NP_001120972.1
MET	NM_001324402.2	c.2625C>A	p.Pro875Pro	synonymous_variant	Exon 19 of 20		NP_001311331.1
MET	XM_011516223.2	c.3972C>A	p.Pro1324Pro	synonymous_variant	Exon 21 of 22		XP_011514525.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MET	ENST00000397752.8	c.3915C>A	p.Pro1305Pro	synonymous_variant	Exon 20 of 21	1	NM_000245.4	ENSP00000380860.3
MET	ENST00000318493.11	c.3969C>A	p.Pro1323Pro	synonymous_variant	Exon 20 of 21	1		ENSP00000317272.6
MET	ENST00000436117.3	n.*1520C>A		non_coding_transcript_exon_variant	Exon 19 of 20	1		ENSP00000410980.2
MET	ENST00000436117.3	n.*1520C>A		3_prime_UTR_variant	Exon 19 of 20	1		ENSP00000410980.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 61

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Hereditary cancer-predisposing syndrome Benign:1

Sep 26, 2021

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	0.23
DANN	Benign	0.53

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: chr7-116435825;