NM_000520.6:c.947dupA
Variant summary
Our verdict is Pathogenic. The variant received 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_000520.6(HEXA):c.947dupA(p.Tyr316fs) variant causes a frameshift, stop gained change. The variant allele was found at a frequency of 0.00000137 in 1,461,812 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (no stars). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_000520.6 frameshift, stop_gained
Scores
Clinical Significance
Conservation
Publications
- Tay-Sachs diseaseInheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Myriad Women’s Health, Genomics England PanelApp, G2P, Labcorp Genetics (formerly Invitae), ClinGen
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ACMG classification
Our verdict: Pathogenic. The variant received 11 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
HEXA | NM_000520.6 | c.947dupA | p.Tyr316fs | frameshift_variant, stop_gained | Exon 8 of 14 | ENST00000268097.10 | NP_000511.2 | |
HEXA | NM_001318825.2 | c.980dupA | p.Tyr327fs | frameshift_variant, stop_gained | Exon 8 of 14 | NP_001305754.1 | ||
HEXA | NR_134869.3 | n.989dupA | non_coding_transcript_exon_variant | Exon 8 of 11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
HEXA | ENST00000268097.10 | c.947dupA | p.Tyr316fs | frameshift_variant, stop_gained | Exon 8 of 14 | 1 | NM_000520.6 | ENSP00000268097.6 | ||
ENSG00000260729 | ENST00000379915.4 | n.413-2793dupA | intron_variant | Intron 3 of 15 | 2 | ENSP00000478716.1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461812Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2AN XY: 727210 show subpopulations
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Tay-Sachs disease Pathogenic:1
This submission and the accompanying classification are no longer maintained by the submitter. For more information on current observations and classification, please contact variantquestions@myriad.com. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at