rs2303448
Positions:
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_000520.6(HEXA):c.1331-46G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0604 in 1,552,948 control chromosomes in the GnomAD database, including 3,249 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.046 ( 224 hom., cov: 32)
Exomes 𝑓: 0.062 ( 3025 hom. )
Consequence
HEXA
NM_000520.6 intron
NM_000520.6 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.50
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.79).
BP6
?
Variant 15-72346371-C-T is Benign according to our data. Variant chr15-72346371-C-T is described in ClinVar as [Benign]. Clinvar id is 256350.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
?
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.11 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HEXA | NM_000520.6 | c.1331-46G>A | intron_variant | ENST00000268097.10 | |||
HEXA | NM_001318825.2 | c.1364-46G>A | intron_variant | ||||
HEXA | NR_134869.3 | n.1116-46G>A | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HEXA | ENST00000268097.10 | c.1331-46G>A | intron_variant | 1 | NM_000520.6 | P1 | |||
ENST00000570175.1 | n.1151C>T | non_coding_transcript_exon_variant | 2/3 | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.0457 AC: 6951AN: 152120Hom.: 225 Cov.: 32
GnomAD3 genomes
?
AF:
AC:
6951
AN:
152120
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.0552 AC: 13624AN: 246764Hom.: 452 AF XY: 0.0575 AC XY: 7674AN XY: 133532
GnomAD3 exomes
AF:
AC:
13624
AN:
246764
Hom.:
AF XY:
AC XY:
7674
AN XY:
133532
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0619 AC: 86774AN: 1400710Hom.: 3025 Cov.: 22 AF XY: 0.0627 AC XY: 43934AN XY: 700494
GnomAD4 exome
AF:
AC:
86774
AN:
1400710
Hom.:
Cov.:
22
AF XY:
AC XY:
43934
AN XY:
700494
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.0456 AC: 6947AN: 152238Hom.: 224 Cov.: 32 AF XY: 0.0447 AC XY: 3325AN XY: 74430
GnomAD4 genome
?
AF:
AC:
6947
AN:
152238
Hom.:
Cov.:
32
AF XY:
AC XY:
3325
AN XY:
74430
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
Asia WGS
AF:
AC:
247
AN:
3478
ClinVar
Significance: Benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Tay-Sachs disease Benign:2
Benign, no assertion criteria provided | clinical testing | Natera, Inc. | Apr 12, 2018 | - - |
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 01, 2021 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Dec 31, 2018 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at