rs934426317

Variant names:

• chr7-116700152-A-G
• rs934426317
• NM_000245.4:c.1068A>G

Your query was ambiguous. Multiple possible variants found:

• chr7-116700152-A-G
• chr7-116700152-A-T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6_Very_Strong BP7

The NM_000245.4(MET):​c.1068A>G​(p.Pro356Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000815 in 1,595,852 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 Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000076 (0 hom.)
• Consequence: MET NM_000245.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.976
• Publications: 0 publications found

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]

COMETT (HGNC:51196): (cytosolic oncogenic antisense to MET transcript) This gene encodes a natural antisense transcript highly expressed in papillary thyroid carcinomas harboring BRAF V600E mutation or RET gene rearrangements. This lncRNA induces the downstream MAPK pathway and is part of a co-expression network including different oncogenes belonging to the MAPK and PI3H/AKT pathways. In thyroid carcinomas, this gene has oncogenic properties associated with increased proliferation and drug resistance. [provided by RefSeq, Jan 2020]

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 7-116700152-A-G is Benign according to our data. Variant chr7-116700152-A-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 454176.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.976 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000245.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MET	NM_000245.4	MANE Select	c.1068A>G	p.Pro356Pro	synonymous	Exon 2 of 21	NP_000236.2
	MET	NM_001127500.3		c.1068A>G	p.Pro356Pro	synonymous	Exon 2 of 21	NP_001120972.1	P08581-2
	MET	NM_001324401.3		c.1068A>G	p.Pro356Pro	synonymous	Exon 2 of 12	NP_001311330.1	E6Y365

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MET	ENST00000397752.8	TSL:1 MANE Select	c.1068A>G	p.Pro356Pro	synonymous	Exon 2 of 21	ENSP00000380860.3	P08581-1
	MET	ENST00000318493.11	TSL:1	c.1068A>G	p.Pro356Pro	synonymous	Exon 2 of 21	ENSP00000317272.6	P08581-2
	MET	ENST00000436117.3	TSL:1	n.1068A>G		non_coding_transcript_exon	Exon 2 of 20	ENSP00000410980.2	P08581-3

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152216 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000762 AC: 11 AN: 1443636 Hom.: 0 Cov.: 32 AF XY: 0.00000977 AC XY: 7 AN XY: 716188

African (AFR) AF: 0.00 AC: 0 AN: 32626

American (AMR) AF: 0.00 AC: 0 AN: 42222

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25010

East Asian (EAS) AF: 0.00 AC: 0 AN: 39536

South Asian (SAS) AF: 0.00 AC: 0 AN: 82542

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52736

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5634

European-Non Finnish (NFE) AF: 0.00000997 AC: 11 AN: 1103778

Other (OTH) AF: 0.00 AC: 0 AN: 59552

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152216 Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1 AN XY: 74362

African (AFR) AF: 0.00 AC: 0 AN: 41472

American (AMR) AF: 0.00 AC: 0 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5202

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68022

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000151

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Hereditary cancer-predisposing syndrome (1)
-	-	1	Papillary renal cell carcinoma type 1 (1)
-	-	1	Renal cell carcinoma (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.46
DANN	Benign	0.45
PhyloP100		-0.98
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

Other links and lift over

dbSNP: rs934426317; hg19: chr7-116340206;