5-74715695-G-C
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP5
The NM_000521.4(HEXB):c.1082+5G>C variant causes a splice region, intron change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Genomes: not found (cov: 31)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
HEXB
NM_000521.4 splice_region, intron
NM_000521.4 splice_region, intron
Scores
2
Splicing: ADA: 0.9998
2
Clinical Significance
Conservation
PhyloP100: 6.29
Genes affected
HEXB (HGNC:4879): (hexosaminidase subunit beta) Hexosaminidase B is the beta subunit of the lysosomal enzyme beta-hexosaminidase that, together with the cofactor GM2 activator protein, catalyzes the degradation of the ganglioside GM2, and other molecules containing terminal N-acetyl hexosamines. Beta-hexosaminidase is composed of two subunits, alpha and beta, which are encoded by separate genes. Both beta-hexosaminidase alpha and beta subunits are members of family 20 of glycosyl hydrolases. Mutations in the alpha or beta subunit genes lead to an accumulation of GM2 ganglioside in neurons and neurodegenerative disorders termed the GM2 gangliosidoses. Beta subunit gene mutations lead to Sandhoff disease (GM2-gangliosidosis type II). Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2014]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 5-74715695-G-C is Pathogenic according to our data. Variant chr5-74715695-G-C is described in ClinVar as [Pathogenic]. Clinvar id is 3885.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes Cov.: 31
GnomAD3 genomes
Cov.:
31
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1402332Hom.: 0 Cov.: 25 AF XY: 0.00 AC XY: 0AN XY: 700702
GnomAD4 exome
Data not reliable, filtered out with message: AC0
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0
AN:
1402332
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Cov.:
25
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0
AN XY:
700702
Gnomad4 AFR exome
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GnomAD4 genome Cov.: 31
GnomAD4 genome
Cov.:
31
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Sandhoff disease, infantile form Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Jan 01, 1999 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Benign
Splicing
Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Pathogenic
dbscSNV1_RF
Pathogenic
SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_DG_spliceai
Position offset: -9
DS_DL_spliceai
Position offset: -5
Find out detailed SpliceAI scores and Pangolin per-transcript scores at