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NM_000520.6(HEXA):c.1305C>T (p.Tyr435=) AND Inborn genetic diseases

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Jun 5, 2024
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV000624856.3

Allele description [Variation Report for NM_000520.6(HEXA):c.1305C>T (p.Tyr435=)]

NM_000520.6(HEXA):c.1305C>T (p.Tyr435=)

Gene:
HEXA:hexosaminidase subunit alpha [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
15q23
Genomic location:
Preferred name:
NM_000520.6(HEXA):c.1305C>T (p.Tyr435=)
HGVS:
  • NC_000015.10:g.72346552G>A
  • NG_009017.2:g.34628C>T
  • NM_000520.6:c.1305C>TMANE SELECT
  • NM_001318825.2:c.1338C>T
  • NP_000511.2:p.Tyr435=
  • NP_001305754.1:p.Tyr446=
  • NC_000015.9:g.72638893G>A
  • NG_009017.1:g.34628C>T
  • NM_000520.4:c.1305C>T
  • NM_000520.5:c.1305C>T
  • p.Tyr435Tyr
Links:
dbSNP: rs587779406
NCBI 1000 Genomes Browser:
rs587779406
Molecular consequence:
  • NM_000520.6:c.1305C>T - synonymous variant - [Sequence Ontology: SO:0001819]
  • NM_001318825.2:c.1338C>T - synonymous variant - [Sequence Ontology: SO:0001819]

Condition(s)

Name:
Inborn genetic diseases
Identifiers:
MeSH: D030342; MedGen: C0950123

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000742704Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Pathogenic
(Jun 5, 2024) 		germlineclinical testing

PubMed (4)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Two novel exonic point mutations in HEXA identified in a juvenile Tay-Sachs patient: role of alternative splicing and nonsense-mediated mRNA decay.

Levit A, Nutman D, Osher E, Kamhi E, Navon R.

Mol Genet Metab. 2010 Jun;100(2):176-83. doi: 10.1016/j.ymgme.2010.03.010. Epub 2010 Mar 19.

PubMed [citation]
PMID:
20363167

GM2 gangliosidoses in Spain: analysis of the HEXA and HEXB genes in 34 Tay-Sachs and 14 Sandhoff patients.

Gort L, de Olano N, Macías-Vidal J, Coll MA; Spanish GM2 Working Group..

Gene. 2012 Sep 10;506(1):25-30. Epub 2012 Jul 10.

PubMed [citation]
PMID:
22789865
See all PubMed Citations (4)

Details of each submission

From Ambry Genetics, SCV000742704.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)

Description

The c.1305C>T (p.Y435Y) alteration is located in coding exon 11 of the HEXA gene. This alteration consists of a C to T substitution at nucleotide position 1305. This nucleotide substitution does not change the amino acid at codon 435. However, further evidence has suggested this nucleotide change is deleterious. Based on data from gnomAD, the T allele has an overall frequency of 0.009% (24/282766) total alleles studied. The highest observed frequency was 0.048% (17/35436) of Latino alleles. This alteration was detected in conjunction with another alteration in HEXA, in multiple individuals with Tay-Sachs disease (Gort, 2012; Fernandez-Marmiesse, 2014; Georgiou, 2014). This nucleotide position is well conserved in available vertebrate species. In an assay testing HEXA function, this variant showed a functionally abnormal result (Levit, 2010). In silico splice site analysis for this alteration is inconclusive. Based on the available evidence, this alteration is classified as pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Aug 11, 2024