VCV000189079.5 - ClinVar

NM_000382.3(ALDH3A2):c.798+5G>A

Germline

Classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

(3)

Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.

Pathogenic/Likely pathogenic

criteria provided, multiple submitters, no conflicts

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_000382.3(ALDH3A2):c.798+5G>A

Variation ID: 189079 Accession: VCV000189079.5

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 17p11.2 17: 19657867 (GRCh38) [ NCBI UCSC ] 17: 19561180 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Mar 29, 2015	Feb 14, 2024	Oct 5, 2022

HGVS

Nucleotide	Protein	Molecular consequence
NM_000382.3:c.798+5G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.		intron variant
NM_001031806.2:c.798+5G>A		intron variant
NM_001369136.1:c.798+5G>A		intron variant
NM_001369137.2:c.798+5G>A		intron variant
NM_001369138.2:c.798+5G>A		intron variant
NM_001369139.1:c.798+5G>A		intron variant
NM_001369146.2:c.798+5G>A		intron variant
NM_001369148.2:c.219+5G>A		intron variant
NC_000017.11:g.19657867G>A
NC_000017.10:g.19561180G>A
NG_007095.2:g.14117G>A

... more HGVS ... less HGVS

Protein change

Other names

Canonical SPDI

NC_000017.11:19657866:G:A

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

Allele frequency Help The frequency of the allele represented by this VCV record.

Links

ClinGen: CA199114 VarSome

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
ALDH3A2		-	-	GRCh38 GRCh37	635	757

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
Sjögren-Larsson syndrome	Likely pathogenic (2)	criteria provided, single submitter	Dec 9, 2014	RCV000169484.4
not provided	Pathogenic (1)	criteria provided, single submitter	Oct 5, 2022	RCV002516533.4

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	More information Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Likely pathogenic (Dec 09, 2014)	criteria provided, single submitter (Counsyl Autosomal and X-linked Recessive Disease Classification criteria (2015)) Method: literature only	Sjögren-Larsson syndrome (Autosomal recessive inheritance) Affected status: unknown Allele origin: unknown	Counsyl Accession: SCV000220936.2 First in ClinVar: Mar 29, 2015 Last updated: Dec 24, 2022	Publications: PubMed (1) PubMed: 10577908
Pathogenic (Oct 05, 2022)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	not provided Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV003442601.2 First in ClinVar: Feb 07, 2023 Last updated: Feb 14, 2024	Publications: PubMed (3) PubMed: 17576681‚ 9536098‚ 10577908 Comment: For these reasons, this variant has been classified as Pathogenic. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing … (more) For these reasons, this variant has been classified as Pathogenic. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Studies have shown that this variant is associated with altered splicing resulting in two abnormal transcripts (PMID: 10577908). ClinVar contains an entry for this variant (Variation ID: 189079). This variant has been observed in individual(s) with Sj√∂gren-Larsson syndrome (PMID: 10577908). This variant is not present in population databases (gnomAD no frequency). This sequence change falls in intron 5 of the ALDH3A2 gene. It does not directly change the encoded amino acid sequence of the ALDH3A2 protein. It affects a nucleotide within the consensus splice site. (less)
Pathogenic (-)	no assertion criteria provided Method: clinical testing	Sjögren-Larsson syndrome (Autosomal recessive inheritance) Affected status: yes Allele origin: inherited	Génétique des Maladies du Développement, Hospices Civils de Lyon Accession: SCV001738833.1 First in ClinVar: Jul 07, 2021 Last updated: Jul 07, 2021

Comment:

For these reasons, this variant has been classified as Pathogenic. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Studies have shown that this variant is associated with altered splicing resulting in two abnormal transcripts (PMID: 10577908). ClinVar contains an entry for this variant (Variation ID: 189079). This variant has been observed in individual(s) with Sj√∂gren-Larsson syndrome (PMID: 10577908). This variant is not present in population databases (gnomAD no frequency). This sequence change falls in intron 5 of the ALDH3A2 gene. It does not directly change the encoded amino acid sequence of the ALDH3A2 protein. It affects a nucleotide within the consensus splice site.

Germline Functional Evidence

There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Comment:

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Aberrant 5' splice sites in human disease genes: mutation pattern, nucleotide structure and comparison of computational tools that predict their utilization.	Buratti E	Nucleic acids research	2007	PMID: 17576681
The molecular basis of Sjögren-Larsson syndrome: mutation analysis of the fatty aldehyde dehydrogenase gene.	Rizzo WB	American journal of human genetics	1999	PMID: 10577908
Statistical features of human exons and their flanking regions.	Zhang MQ	Human molecular genetics	1998	PMID: 9536098

Text-mined citations for this variant ...

Record last updated Sep 29, 2024

ClinVar Genomic variation as it relates to human health

NM_000382.3(ALDH3A2):c.798+5G>A

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...