rs573447174
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Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate
The NM_000521.4(HEXB):āc.552T>Cā(p.Tyr184=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000418 in 1,436,982 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ).
Frequency
Genomes: š 0.000033 ( 0 hom., cov: 33)
Exomes š: 7.8e-7 ( 0 hom. )
Consequence
HEXB
NM_000521.4 synonymous
NM_000521.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.833
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 Likely_benign. Variant got -4 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.68).
BP6
?
Variant 5-74696733-T-C is Benign according to our data. Variant chr5-74696733-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 1589107.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HEXB | NM_000521.4 | c.552T>C | p.Tyr184= | synonymous_variant | 4/14 | ENST00000261416.12 | |
HEXB | NM_001292004.2 | c.-124T>C | 5_prime_UTR_variant | 4/14 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HEXB | ENST00000261416.12 | c.552T>C | p.Tyr184= | synonymous_variant | 4/14 | 1 | NM_000521.4 | P1 | |
HEXB | ENST00000511181.5 | c.-124T>C | 5_prime_UTR_variant | 4/14 | 1 | ||||
HEXB | ENST00000510820.1 | n.271T>C | non_coding_transcript_exon_variant | 2/4 | 3 | ||||
HEXB | ENST00000513079.5 | n.617T>C | non_coding_transcript_exon_variant | 4/6 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000329 AC: 5AN: 152174Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.00000405 AC: 1AN: 246712Hom.: 0 AF XY: 0.00000748 AC XY: 1AN XY: 133640
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GnomAD4 exome AF: 7.78e-7 AC: 1AN: 1284808Hom.: 0 Cov.: 20 AF XY: 0.00000154 AC XY: 1AN XY: 648292
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GnomAD4 genome ? AF: 0.0000329 AC: 5AN: 152174Hom.: 0 Cov.: 33 AF XY: 0.0000538 AC XY: 4AN XY: 74352
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Sandhoff disease Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Aug 17, 2023 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at