chr8-18064501-T-C
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PM1PM2PM5PP3_StrongPP5_Moderate
The NM_177924.5(ASAH1):c.413A>G(p.Glu138Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E138V) has been classified as Likely pathogenic.
Frequency
Consequence
NM_177924.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ASAH1 | NM_177924.5 | c.413A>G | p.Glu138Gly | missense_variant | 6/14 | ENST00000637790.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ASAH1 | ENST00000637790.2 | c.413A>G | p.Glu138Gly | missense_variant | 6/14 | 1 | NM_177924.5 | P2 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome Cov.: 28
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Farber lipogranulomatosis Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Diagnostics Services (NGS), CSIR - Centre For Cellular And Molecular Biology | May 20, 2022 | The c.461A>G variant is not present in publicly available population databases like 1000 Genomes, Exome Variant Server (EVS), Exome Aggregation Consortium (ExAC), Genome Aggregation Database (gnomAD) and dbSNP. The variant is not present in Indian Exome Database and in our in-house exome database. The variant was not previously reported to ClinVar, Human Genome Mutation Database (HGMD) and/or OMIM databases in any affected individuals. In-silico pathogenicity prediction programs like SIFT, PolyPhen-2, MutationTaster2, CADD, Varsome, InterVar etc. predicted this variant to be likely deleterious. The variant is located in a dense mutational hotspot region of the gene where other pathogenic missense variants has been identified and reported. An alternative variant in the same position (c.461A>T, p.Glu154Val) was previously reported to ClinVar (Accession: VCV000000092.2) and HGMD (ID: CM993321) as pathogenic/likely pathogenic in association with Farber disease (PMID: 10610716). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.