chr17-19656414-CT-C

Variant names:

• chr17-19656414-CT-C
• rs387906254
• NM_000382.3:c.521delT

Variant summary

Our verdict is Pathogenic. The variant received 11 ACMG points: 11P and 0B. PVS1 PM2 PP5

The NM_000382.3(ALDH3A2):​c.521delT​(p.Leu174ArgfsTer28) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars). Synonymous variant affecting the same amino acid position (i.e. L174L) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ALDH3A2 NM_000382.3 frameshift
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 7.98
• Publications: 1 publications found

Genes affected

ALDH3A2 (HGNC:403): (aldehyde dehydrogenase 3 family member A2) Aldehyde dehydrogenase isozymes are thought to play a major role in the detoxification of aldehydes generated by alcohol metabolism and lipid peroxidation. This gene product catalyzes the oxidation of long-chain aliphatic aldehydes to fatty acid. Mutations in the gene cause Sjogren-Larsson syndrome. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ALDH3A2 Gene-Disease associations (from GenCC):

• Sjogren-Larsson syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Myriad Women’s Health, PanelApp Australia, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Pathogenic. The variant received 11 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 17-19656414-CT-C is Pathogenic according to our data. Variant chr17-19656414-CT-C is described in CliVar as Pathogenic. Clinvar id is 1636.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr17-19656414-CT-C is described in CliVar as Pathogenic. Clinvar id is 1636.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr17-19656414-CT-C is described in CliVar as Pathogenic. Clinvar id is 1636.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr17-19656414-CT-C is described in CliVar as Pathogenic. Clinvar id is 1636.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr17-19656414-CT-C is described in CliVar as Pathogenic. Clinvar id is 1636.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr17-19656414-CT-C is described in CliVar as Pathogenic. Clinvar id is 1636.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr17-19656414-CT-C is described in CliVar as Pathogenic. Clinvar id is 1636.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr17-19656414-CT-C is described in CliVar as Pathogenic. Clinvar id is 1636.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr17-19656414-CT-C is described in CliVar as Pathogenic. Clinvar id is 1636.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr17-19656414-CT-C is described in CliVar as Pathogenic. Clinvar id is 1636.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr17-19656414-CT-C is described in CliVar as Pathogenic. Clinvar id is 1636.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr17-19656414-CT-C is described in CliVar as Pathogenic. Clinvar id is 1636.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr17-19656414-CT-C is described in CliVar as Pathogenic. Clinvar id is 1636.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr17-19656414-CT-C is described in CliVar as Pathogenic. Clinvar id is 1636.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr17-19656414-CT-C is described in CliVar as Pathogenic. Clinvar id is 1636.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr17-19656414-CT-C is described in CliVar as Pathogenic. Clinvar id is 1636.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr17-19656414-CT-C is described in CliVar as Pathogenic. Clinvar id is 1636.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr17-19656414-CT-C is described in CliVar as Pathogenic. Clinvar id is 1636.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr17-19656414-CT-C is described in CliVar as Pathogenic. Clinvar id is 1636.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr17-19656414-CT-C is described in CliVar as Pathogenic. Clinvar id is 1636.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr17-19656414-CT-C is described in CliVar as Pathogenic. Clinvar id is 1636.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr17-19656414-CT-C is described in CliVar as Pathogenic. Clinvar id is 1636.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr17-19656414-CT-C is described in CliVar as Pathogenic. Clinvar id is 1636.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr17-19656414-CT-C is described in CliVar as Pathogenic. Clinvar id is 1636.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr17-19656414-CT-C is described in CliVar as Pathogenic. Clinvar id is 1636.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr17-19656414-CT-C is described in CliVar as Pathogenic. Clinvar id is 1636.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr17-19656414-CT-C is described in CliVar as Pathogenic. Clinvar id is 1636.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr17-19656414-CT-C is described in CliVar as Pathogenic. Clinvar id is 1636.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr17-19656414-CT-C is described in CliVar as Pathogenic. Clinvar id is 1636.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr17-19656414-CT-C is described in CliVar as Pathogenic. Clinvar id is 1636.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr17-19656414-CT-C is described in CliVar as Pathogenic. Clinvar id is 1636.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr17-19656414-CT-C is described in CliVar as Pathogenic. Clinvar id is 1636.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALDH3A2	NM_000382.3	c.521delT	p.Leu174ArgfsTer28	frameshift_variant	Exon 4 of 10	ENST00000176643.11	NP_000373.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALDH3A2	ENST00000176643.11	c.521delT	p.Leu174ArgfsTer28	frameshift_variant	Exon 4 of 10	1	NM_000382.3	ENSP00000176643.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Sjögren-Larsson syndrome Pathogenic:1

Jan 01, 1996

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		8.0
Mutation Taster		=0/200	disease causing (ClinVar)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs387906254; hg19: chr17-19559727;