rs3087652
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Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1
The NM_000520.6(HEXA):c.*515G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.754 in 162,730 control chromosomes in the GnomAD database, including 52,573 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.74 ( 48315 hom., cov: 32)
Exomes 𝑓: 0.89 ( 4258 hom. )
Consequence
HEXA
NM_000520.6 3_prime_UTR
NM_000520.6 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.0290
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 Benign. Variant got -14 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
BP6
?
Variant 15-72343562-C-T is Benign according to our data. Variant chr15-72343562-C-T is described in ClinVar as [Benign]. Clinvar id is 317035.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
?
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.935 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HEXA | NM_000520.6 | c.*515G>A | 3_prime_UTR_variant | 14/14 | ENST00000268097.10 | ||
HEXA | NM_001318825.2 | c.*515G>A | 3_prime_UTR_variant | 14/14 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HEXA | ENST00000268097.10 | c.*515G>A | 3_prime_UTR_variant | 14/14 | 1 | NM_000520.6 | P1 | ||
ENST00000570175.1 | n.166-1824C>T | intron_variant, non_coding_transcript_variant | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.745 AC: 113253AN: 151962Hom.: 48331 Cov.: 32
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GnomAD4 exome AF: 0.886 AC: 9436AN: 10650Hom.: 4258 Cov.: 0 AF XY: 0.891 AC XY: 5036AN XY: 5654
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GnomAD4 genome ? AF: 0.745 AC: 113244AN: 152080Hom.: 48315 Cov.: 32 AF XY: 0.750 AC XY: 55730AN XY: 74348
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Tay-Sachs disease Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at