rs763933267

Variant names:

• chr7-81702663-C-A
• rs763933267
• NM_000601.6:c.2105G>T

Your query was ambiguous. Multiple possible variants found:

• chr7-81702663-C-A
• chr7-81702663-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_000601.6(HGF):​c.2105G>T​(p.Arg702Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000206 in 1,459,798 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: HGF NM_000601.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.39

Genes affected

HGF (HGNC:4893): (hepatocyte growth factor) This gene encodes a protein that binds to the hepatocyte growth factor receptor to regulate cell growth, cell motility and morphogenesis in numerous cell and tissue types. Alternative splicing results in multiple transcript variants, at least one of which encodes a preproprotein that is proteolytically processed to generate alpha and beta chains, which form the mature heterodimer. This protein is secreted by mesenchymal cells and acts as a multi-functional cytokine on cells of mainly epithelial origin. This protein also plays a role in angiogenesis, tumorogenesis, and tissue regeneration. Although the encoded protein is a member of the peptidase S1 family of serine proteases, it lacks peptidase activity. Mutations in this gene are associated with nonsyndromic hearing loss. [provided by RefSeq, Nov 2015]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.905

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HGF	NM_000601.6	c.2105G>T	p.Arg702Leu	missense_variant	Exon 18 of 18	ENST00000222390.11	NP_000592.3
HGF	NM_001010932.3	c.2090G>T	p.Arg697Leu	missense_variant	Exon 18 of 18		NP_001010932.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HGF	ENST00000222390.11	c.2105G>T	p.Arg702Leu	missense_variant	Exon 18 of 18	1	NM_000601.6	ENSP00000222390.5
HGF	ENST00000457544.7	c.2090G>T	p.Arg697Leu	missense_variant	Exon 18 of 18	1		ENSP00000391238.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000206 AC: 3 AN: 1459798 Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2 AN XY: 726246

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000270

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.56
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Uncertain	0.090
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.83	D;D;.
Eigen	Uncertain	0.60
Eigen_PC	Uncertain	0.63
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.92	.;D;D
M_CAP	Uncertain	0.091	D
MetaRNN	Pathogenic	0.90	D;D;D
MetaSVM	Uncertain	0.55	D
MutationAssessor	Benign	0.18	N;N;.
PrimateAI	Uncertain	0.73	T
PROVEAN	Uncertain	-3.5	.;D;D
REVEL	Pathogenic	0.72
Sift	Benign	0.13	.;T;T
Sift4G	Benign	0.12	.;T;T
Polyphen		1.0	D;D;D
Vest4		0.54, 0.69
MutPred		0.80		Loss of methylation at R702 (P = 0.0256);Loss of methylation at R702 (P = 0.0256);.;
MVP		0.90
MPC		1.6
ClinPred		0.99	D
GERP RS		5.3
Varity_R		0.76
gMVP		0.84

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs763933267; hg19: chr7-81331979;