17-19671818-T-TAACAA
Position:
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_000382.3(ALDH3A2):c.1307_1311dup(p.Leu438ThrfsTer21) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000616 in 1,461,868 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000062 ( 0 hom. )
Consequence
ALDH3A2
NM_000382.3 frameshift
NM_000382.3 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 7.93
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 18 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 17-19671818-T-TAACAA is Pathogenic according to our data. Variant chr17-19671818-T-TAACAA is described in ClinVar as [Pathogenic]. Clinvar id is 1642.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ALDH3A2 | NM_000382.3 | c.1307_1311dup | p.Leu438ThrfsTer21 | frameshift_variant | 9/10 | ENST00000176643.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ALDH3A2 | ENST00000176643.11 | c.1307_1311dup | p.Leu438ThrfsTer21 | frameshift_variant | 9/10 | 1 | NM_000382.3 | P1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome AF: 0.00000616 AC: 9AN: 1461868Hom.: 0 Cov.: 32 AF XY: 0.00000688 AC XY: 5AN XY: 727242
GnomAD4 exome
AF:
AC:
9
AN:
1461868
Hom.:
Cov.:
32
AF XY:
AC XY:
5
AN XY:
727242
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Sjögren-Larsson syndrome Pathogenic:2
Pathogenic, no assertion criteria provided | literature only | OMIM | May 01, 1997 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Counsyl | Mar 05, 2018 | - - |
not provided Pathogenic:2
Likely pathogenic, no assertion criteria provided | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | Mar 10, 2016 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Jun 27, 2022 | ClinVar contains an entry for this variant (Variation ID: 1642). This variant is also known as 1311insACAAA. This premature translational stop signal has been observed in individual(s) with Sjogren-Larsson syndrome (PMID: 9250352). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Leu438Thrfs*21) in the ALDH3A2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ALDH3A2 are known to be pathogenic (PMID: 10577908, 10854114). For these reasons, this variant has been classified as Pathogenic. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at