rs773446161
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The ENST00000268097.10(HEXA):c.316C>T(p.Gln106Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,762 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
ENST00000268097.10 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
HEXA | NM_000520.6 | c.316C>T | p.Gln106Ter | stop_gained | 2/14 | ENST00000268097.10 | NP_000511.2 | |
HEXA | NM_001318825.2 | c.349C>T | p.Gln117Ter | stop_gained | 2/14 | NP_001305754.1 | ||
HEXA | NR_134869.3 | n.358C>T | non_coding_transcript_exon_variant | 2/11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
HEXA | ENST00000268097.10 | c.316C>T | p.Gln106Ter | stop_gained | 2/14 | 1 | NM_000520.6 | ENSP00000268097 | P1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251378Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135868
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461762Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 727186
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Tay-Sachs disease Pathogenic:4
Likely pathogenic, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Nov 01, 2021 | - - |
Likely pathogenic, criteria provided, single submitter | clinical testing | Counsyl | Jan 31, 2018 | - - |
Pathogenic, no assertion criteria provided | research | Foundation for Research in Genetics and Endocrinology, FRIGE's Institute of Human Genetics | Jun 17, 2014 | - - |
Likely pathogenic, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Mar 21, 2022 | Variant summary: HEXA c.316C>T (p.Gln106X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant allele was found at a frequency of 4e-06 in 251378 control chromosomes (gnomAD). c.316C>T has been reported in the literature in at least one individual affected with Tay-Sachs Disease (Mistri_2019) and one obligate carrier (Akerman_1997). These data do not allow any conclusion about variant significance. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two ClinVar submitters have assessed the variant since 2014: both classified the variant as likely pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at