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NM_006415.4(SPTLC1):c.431T>A (p.Val144Asp) AND SPTLC1-related disorder

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Mar 14, 2024
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
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:
RCV004755711.1

Allele description [Variation Report for NM_006415.4(SPTLC1):c.431T>A (p.Val144Asp)]

NM_006415.4(SPTLC1):c.431T>A (p.Val144Asp)

Gene:
SPTLC1:serine palmitoyltransferase long chain base subunit 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
9q22.31
Genomic location:
Preferred name:
NM_006415.4(SPTLC1):c.431T>A (p.Val144Asp)
HGVS:
  • NC_000009.12:g.92068095A>T
  • NG_007950.1:g.52314T>A
  • NM_001281303.2:c.431T>A
  • NM_001368272.1:c.65T>A
  • NM_001368273.1:c.-35T>A
  • NM_006415.4:c.431T>AMANE SELECT
  • NP_001268232.1:p.Val144Asp
  • NP_001355201.1:p.Val22Asp
  • NP_006406.1:p.Val144Asp
  • LRG_272t1:c.431T>A
  • LRG_272:g.52314T>A
  • LRG_272p1:p.Val144Asp
  • NC_000009.11:g.94830377A>T
  • NM_006415.2:c.431T>A
  • NM_006415.3:c.431T>A
  • O15269:p.Val144Asp
Protein change:
V144D; VAL144ASP
Links:
UniProtKB: O15269#VAR_011394; OMIM: 605712.0003; dbSNP: rs119482083
NCBI 1000 Genomes Browser:
rs119482083
Molecular consequence:
  • NM_001368273.1:c.-35T>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001281303.2:c.431T>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001368272.1:c.65T>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_006415.4:c.431T>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
SPTLC1-related disorder
Synonyms:
SPTLC1-related condition
Identifiers:

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV005350680PreventionGenetics, part of Exact Sciences
no assertion criteria provided
Likely pathogenic
(Mar 14, 2024) 		germlineclinical testing

Help

Summary from all submissions

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

Details of each submission

From PreventionGenetics, part of Exact Sciences, SCV005350680.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

The SPTLC1 c.431T>A variant is predicted to result in the amino acid substitution p.Val144Asp. This variant has been reported in multiple individuals with hereditary sensory neuropathy (Table 2, Dawkins et al. 2001. PubMed ID: 11242114; Ho and Jerath. 2018. PubMed ID: 30420926; Table 1, Vogt et al. 2020. PubMed ID: 32399692). This variant is reported in 0.0018% of alleles in individuals of European (non-Finnish) descent in gnomAD. In vitro experimental studies suggest this variant decreases enzymatic activity of the protein and negatively regulates the BiP pathway (Hornemann et al. 2009. PubMed ID: 19132419; Myers et al. 2014. PubMed ID: 24673574). This variant is interpreted as pathogenic or likely pathogenic by multiple submitters to ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/4801/). In summary, this variant is interpreted as likely pathogenic.

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

Last Updated: Oct 13, 2024