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NM_000382.3(ALDH3A2):c.681-14T>G AND not provided

Germline classification:
Conflicting interpretations of pathogenicity (2 submissions)
Last evaluated:
Apr 12, 2022
Review status:
criteria provided, conflicting classifications
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:
RCV000521423.4

Allele description [Variation Report for NM_000382.3(ALDH3A2):c.681-14T>G]

NM_000382.3(ALDH3A2):c.681-14T>G

Gene:
ALDH3A2:aldehyde dehydrogenase 3 family member A2 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
17p11.2
Genomic location:
Preferred name:
NM_000382.3(ALDH3A2):c.681-14T>G
HGVS:
  • NC_000017.11:g.19657731T>G
  • NG_007095.2:g.13981T>G
  • NM_000382.3:c.681-14T>GMANE SELECT
  • NM_001031806.2:c.681-14T>G
  • NM_001369136.1:c.681-14T>G
  • NM_001369137.2:c.681-14T>G
  • NM_001369138.2:c.681-14T>G
  • NM_001369139.1:c.681-14T>G
  • NM_001369146.2:c.681-14T>G
  • NM_001369148.2:c.102-14T>G
  • NC_000017.10:g.19561044T>G
  • NM_000382.2:c.681-14T>G
Links:
dbSNP: rs1400349287
NCBI 1000 Genomes Browser:
rs1400349287
Molecular consequence:
  • NM_000382.3:c.681-14T>G - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001031806.2:c.681-14T>G - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001369136.1:c.681-14T>G - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001369137.2:c.681-14T>G - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001369138.2:c.681-14T>G - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001369139.1:c.681-14T>G - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001369146.2:c.681-14T>G - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001369148.2:c.102-14T>G - intron variant - [Sequence Ontology: SO:0001627]

Condition(s)

Synonyms:
none provided
Identifiers:
MedGen: C3661900

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000617641GeneDx
criteria provided, single submitter

(GeneDx Variant Classification (06012015))		Likely pathogenic
(Aug 31, 2017) 		germlineclinical testing

Citation Link,

SCV003441681Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Apr 12, 2022) 		germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

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

Citations

PubMed

Sjögren-Larsson syndrome: optical coherence tomography and a novel mutation.

Burgueño-Montañés C, García-Fernández M, Colunga-Cueva M, García-López A.

Arch Soc Esp Oftalmol. 2014 Dec;89(12):504-7. doi: 10.1016/j.oftal.2013.11.010. Epub 2013 Dec 27. English, Spanish.

PubMed [citation]
PMID:
24377952

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240-242.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From GeneDx, SCV000617641.1

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

Description

The c.681-14 T>G splice site variant has been previously reported in association with Sjögren-Larsson syndrome (Burgueño-Montañés et al., 2014). The variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). This variant occurs at a nucleotide that is not conserved; however, several in-silico splice prediction models predict that c.681-14 T>G reduces the strength of the splice acceptor site of intron 4. Additionally, another variant at the same nucleotide has been reported in the Human Gene Mutation Database in association with Sjoegren-Larsson syndrome (Stenson et al., 2014). In the absence of RNA/functional studies, the actual effect of this sequence change in this individual is unknown. In summary, we consider this variant to be likely pathogenic.

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

From Invitae, SCV003441681.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

This sequence change falls in intron 4 of the ALDH3A2 gene. It does not directly change the encoded amino acid sequence of the ALDH3A2 protein. This variant is present in population databases (no rsID available, gnomAD 0.004%). This variant has been observed in individual(s) with Sjögren–Larsson syndrome (PMID: 24377952). ClinVar contains an entry for this variant (Variation ID: 449458). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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

Last Updated: Feb 14, 2024