rs1057519463
Positions:
Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_000520.6(HEXA):c.898_905del(p.Phe300HisfsTer21) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars). Synonymous variant affecting the same amino acid position (i.e. F300F) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Consequence
HEXA
NM_000520.6 frameshift
NM_000520.6 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 9.21
Genes affected
HEXA (HGNC:4878): (hexosaminidase subunit alpha) This gene encodes a member of the glycosyl hydrolase 20 family of proteins. The encoded preproprotein is proteolytically processed to generate the alpha subunit of the lysosomal enzyme beta-hexosaminidase. This enzyme, together with the cofactor GM2 activator protein, catalyzes the degradation of the ganglioside GM2, and other molecules containing terminal N-acetyl hexosamines. Mutations in this gene lead to an accumulation of GM2 ganglioside in neurons, the underlying cause of neurodegenerative disorders termed the GM2 gangliosidoses, including Tay-Sachs disease (GM2-gangliosidosis type I). Alternative splicing results in multiple transcript variants, at least one of which encodes a preproprotein that is proteolytically processed. [provided by RefSeq, Jan 2016]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 11 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 15-72349159-GCTCATGAA-G is Pathogenic according to our data. Variant chr15-72349159-GCTCATGAA-G is described in ClinVar as [Pathogenic]. Clinvar id is 375359.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HEXA | NM_000520.6 | c.898_905del | p.Phe300HisfsTer21 | frameshift_variant | 8/14 | ENST00000268097.10 | |
HEXA | NM_001318825.2 | c.931_938del | p.Phe311HisfsTer21 | frameshift_variant | 8/14 | ||
HEXA | NR_134869.3 | n.940_947del | non_coding_transcript_exon_variant | 8/11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HEXA | ENST00000268097.10 | c.898_905del | p.Phe300HisfsTer21 | frameshift_variant | 8/14 | 1 | NM_000520.6 | P1 | |
ENST00000570175.1 | n.1578-1059_1578-1052del | intron_variant, non_coding_transcript_variant | 1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Tay-Sachs disease Pathogenic:1
Pathogenic, no assertion criteria provided | research | Foundation for Research in Genetics and Endocrinology, FRIGE's Institute of Human Genetics | Sep 07, 2012 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at