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NM_003002.4(SDHD):c.432T>A (p.Tyr144Ter) AND Hereditary cancer-predisposing syndrome

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Nov 14, 2016
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:
RCV000570998.4

Allele description [Variation Report for NM_003002.4(SDHD):c.432T>A (p.Tyr144Ter)]

NM_003002.4(SDHD):c.432T>A (p.Tyr144Ter)

Gene:
SDHD:succinate dehydrogenase complex subunit D [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
11q23.1
Genomic location:
Preferred name:
NM_003002.4(SDHD):c.432T>A (p.Tyr144Ter)
HGVS:
  • NC_000011.10:g.112094922T>A
  • NG_012337.3:g.13076T>A
  • NM_001276503.2:c.*29T>A
  • NM_001276504.2:c.315T>A
  • NM_001276506.2:c.*130T>A
  • NM_003002.4:c.432T>AMANE SELECT
  • NP_001263433.1:p.Tyr105Ter
  • NP_002993.1:p.Tyr144Ter
  • LRG_9t1:c.432T>A
  • LRG_9:g.13076T>A
  • LRG_9p1:p.Tyr144Ter
  • NC_000011.9:g.111965646T>A
  • NM_003002.2:c.432T>A
  • NR_077060.2:n.521T>A
Protein change:
Y105*
Links:
dbSNP: rs1355803189
NCBI 1000 Genomes Browser:
rs1355803189
Molecular consequence:
  • NM_001276503.2:c.*29T>A - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
  • NM_001276506.2:c.*130T>A - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
  • NR_077060.2:n.521T>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NM_001276504.2:c.315T>A - nonsense - [Sequence Ontology: SO:0001587]
  • NM_003002.4:c.432T>A - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:
Hereditary cancer-predisposing syndrome
Synonyms:
Neoplastic Syndromes, Hereditary; Tumor predisposition; Cancer predisposition; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0015356; MeSH: D009386; MedGen: C0027672

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000664521Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Uncertain significance
(Nov 14, 2016) 		germlineclinical testing

Citation Link

Help

Summary from all submissions

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

Details of each submission

From Ambry Genetics, SCV000664521.5

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

Description

The p.Y144* variant (also known as c.432T>A), located in coding exon 4 of the SDHD gene, results from a T to A substitution at nucleotide position 432. This changes the amino acid from a tyrosine to a stop codon within coding exon 4. Premature stop codons are typically deleterious in nature, however, this stop codon occurs at the 3' terminus of SDHD, is not expected to trigger nonsense-mediated mRNA decay, and removes only the last 16 amino acids of the protein. The exact functional impact of these removed amino acids is unknown at this time; however, internal structural analysis suggests that this truncation, which occurs in an important functional domain, would cause significant destabilization of the SDHD protein. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6412 samples (12824 alleles) with coverage at this position. To date, this alteration has been detected with an allele frequency of approximately 0.005% (greater than 20000 alleles tested) in our clinical cohort. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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

Last Updated: May 1, 2024