rs781059624
Variant names:
Variant summary
Our verdict is Pathogenic. The variant received 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_000382.3(ALDH3A2):c.1291_1292delAA(p.Lys431GlufsTer5) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,890 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: 0.0000034 ( 0 hom. )
Consequence
ALDH3A2
NM_000382.3 frameshift
NM_000382.3 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 2.57
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 syndromeInheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Myriad Women’s Health, G2P, Labcorp Genetics (formerly Invitae), Orphanet
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ACMG classification
Classification was made for transcript
Our verdict: Pathogenic. The variant received 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 17-19671802-TAA-T is Pathogenic according to our data. Variant chr17-19671802-TAA-T is described in ClinVar as Pathogenic. ClinVar VariationId is 495850.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_000382.3. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| ALDH3A2 | MANE Select | c.1291_1292delAA | p.Lys431GlufsTer5 | frameshift | Exon 9 of 10 | NP_000373.1 | P51648-1 | ||
| ALDH3A2 | c.1291_1292delAA | p.Lys431GlufsTer5 | frameshift | Exon 9 of 11 | NP_001026976.1 | P51648-2 | |||
| ALDH3A2 | c.1291_1292delAA | p.Lys431GlufsTer5 | frameshift | Exon 10 of 12 | NP_001356065.1 | P51648-2 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| ALDH3A2 | TSL:1 MANE Select | c.1291_1292delAA | p.Lys431GlufsTer5 | frameshift | Exon 9 of 10 | ENSP00000176643.6 | P51648-1 | ||
| ALDH3A2 | TSL:1 | c.1291_1292delAA | p.Lys431GlufsTer5 | frameshift | Exon 9 of 11 | ENSP00000345774.4 | P51648-2 | ||
| ALDH3A2 | TSL:1 | n.1041_1042delAA | non_coding_transcript_exon | Exon 6 of 7 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD4 exome AF: 0.00000342 AC: 5AN: 1461890Hom.: 0 AF XY: 0.00000413 AC XY: 3AN XY: 727246 show subpopulations
GnomAD4 exome
AF:
AC:
5
AN:
1461890
Hom.:
AF XY:
AC XY:
3
AN XY:
727246
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33480
American (AMR)
AF:
AC:
0
AN:
44724
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26136
East Asian (EAS)
AF:
AC:
5
AN:
39700
South Asian (SAS)
AF:
AC:
0
AN:
86258
European-Finnish (FIN)
AF:
AC:
0
AN:
53420
Middle Eastern (MID)
AF:
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
AC:
0
AN:
1112008
Other (OTH)
AF:
AC:
0
AN:
60396
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.485
Heterozygous variant carriers
0
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2
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0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
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10
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>80
Age
GnomAD4 genome
GnomAD4 genome
Cov.:
32
ClinVar
ClinVar submissions
View on ClinVar Significance:Pathogenic
Revision:criteria provided, multiple submitters, no conflicts
Pathogenic
VUS
Benign
Condition
4
-
-
Sjögren-Larsson syndrome (4)
1
-
-
not provided (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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