chr7-81752250-C-T
Variant names:
Variant summary
Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PP3PP5
The NM_000601.6(HGF):c.495G>A(p.Ser165Ser) variant causes a synonymous change. The variant allele was found at a frequency of 0.00000342 in 1,461,140 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 Pathogenic (no stars).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000034 ( 0 hom. )
Consequence
HGF
NM_000601.6 synonymous
NM_000601.6 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 5.36
Publications
4 publications found
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]
HGF Gene-Disease associations (from GenCC):
- autosomal recessive nonsyndromic hearing loss 39Inheritance: AR, Unknown Classification: STRONG, LIMITED Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae), PanelApp Australia
- nonsyndromic genetic hearing lossInheritance: AR Classification: MODERATE Submitted by: ClinGen
- hearing loss, autosomal recessiveInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Uncertain_significance. The variant received 4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.
PP5
Variant 7-81752250-C-T is Pathogenic according to our data. Variant chr7-81752250-C-T is described in ClinVar as Pathogenic. ClinVar VariationId is 14949.Status of the report is no_assertion_criteria_provided, 0 stars.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_000601.6. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| HGF | NM_000601.6 | MANE Select | c.495G>A | p.Ser165Ser | synonymous | Exon 5 of 18 | NP_000592.3 | ||
| HGF | NM_001010931.3 | c.495G>A | p.Ser165Ser | synonymous | Exon 5 of 8 | NP_001010931.1 | |||
| HGF | NM_001010934.3 | c.495G>A | p.Ser165Ser | synonymous | Exon 5 of 5 | NP_001010934.1 |
Ensembl Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| HGF | ENST00000222390.11 | TSL:1 MANE Select | c.495G>A | p.Ser165Ser | synonymous | Exon 5 of 18 | ENSP00000222390.5 | ||
| HGF | ENST00000444829.7 | TSL:1 | c.495G>A | p.Ser165Ser | synonymous | Exon 5 of 8 | ENSP00000389854.2 | ||
| HGF | ENST00000423064.7 | TSL:1 | c.495G>A | p.Ser165Ser | synonymous | Exon 5 of 5 | ENSP00000413829.2 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD2 exomes AF: 0.00000400 AC: 1AN: 249906 AF XY: 0.00 show subpopulations
GnomAD2 exomes
AF:
AC:
1
AN:
249906
AF XY:
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00000342 AC: 5AN: 1461140Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3AN XY: 726898 show subpopulations
GnomAD4 exome
AF:
AC:
5
AN:
1461140
Hom.:
Cov.:
31
AF XY:
AC XY:
3
AN XY:
726898
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33450
American (AMR)
AF:
AC:
2
AN:
44712
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26114
East Asian (EAS)
AF:
AC:
0
AN:
39684
South Asian (SAS)
AF:
AC:
1
AN:
86242
European-Finnish (FIN)
AF:
AC:
0
AN:
53408
Middle Eastern (MID)
AF:
AC:
0
AN:
5766
European-Non Finnish (NFE)
AF:
AC:
2
AN:
1111402
Other (OTH)
AF:
AC:
0
AN:
60362
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.465
Heterozygous variant carriers
0
1
1
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2
3
0.00
0.20
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0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
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Age
GnomAD4 genome
GnomAD4 genome
Cov.:
32
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Autosomal recessive nonsyndromic hearing loss 39 Pathogenic:1
Jul 01, 2009
OMIM
Significance:Pathogenic
Review Status:no assertion criteria provided
Collection Method:literature only
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_AG_spliceai
Position offset: -3
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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