rs1060504945

Positions:

• chr7-116771839-C-A
• chr7-116771839-C-G
• chr7-116771839-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_000245.4(MET):​c.2888-10C>A variant causes a splice polypyrimidine tract, intron 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 splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.9396
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.590

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.21).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MET	NM_000245.4	c.2888-10C>A		splice_polypyrimidine_tract_variant, intron_variant		ENST00000397752.8	NP_000236.2
MET	NM_001127500.3	c.2942-10C>A		splice_polypyrimidine_tract_variant, intron_variant			NP_001120972.1
MET	NM_001324402.2	c.1598-10C>A		splice_polypyrimidine_tract_variant, intron_variant			NP_001311331.1
MET	XM_011516223.2	c.2945-10C>A		splice_polypyrimidine_tract_variant, intron_variant			XP_011514525.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MET	ENST00000397752.8	c.2888-10C>A		splice_polypyrimidine_tract_variant, intron_variant		1	NM_000245.4	ENSP00000380860	P3
MET	ENST00000318493.11	c.2942-10C>A		splice_polypyrimidine_tract_variant, intron_variant		1		ENSP00000317272	A2
MET	ENST00000436117.3	c.*493-10C>A		splice_polypyrimidine_tract_variant, intron_variant, NMD_transcript_variant		1		ENSP00000410980
MET	ENST00000454623.1	c.283+185C>A		intron_variant		5		ENSP00000398140

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.21
CADD	Benign	19
DANN	Benign	0.74

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.94
dbscSNV1_RF	Benign	0.62
SpliceAI score (max)		0.090		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: chr7-116411893;