rs763933267
Variant names:
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_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
NM_000601.6 missense
Scores
4
11
4
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]
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ACMG classification
Classification made for transcript
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
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
GnomAD3 genomes
Cov.:
32
GnomAD4 exome AF: 0.00000206 AC: 3AN: 1459798Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2AN XY: 726246
GnomAD4 exome
AF:
AC:
3
AN:
1459798
Hom.:
Cov.:
30
AF XY:
AC XY:
2
AN XY:
726246
Gnomad4 AFR exome
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GnomAD4 genome
GnomAD4 genome
Cov.:
32
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Pathogenic
D;D;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
.;D;D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D;D
MetaSVM
Uncertain
D
MutationAssessor
Benign
N;N;.
PrimateAI
Uncertain
T
PROVEAN
Uncertain
.;D;D
REVEL
Pathogenic
Sift
Benign
.;T;T
Sift4G
Benign
.;T;T
Polyphen
D;D;D
Vest4
0.54, 0.69
MutPred
Loss of methylation at R702 (P = 0.0256);Loss of methylation at R702 (P = 0.0256);.;
MVP
0.90
MPC
1.6
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at