NM_000691.5:c.382G>C

Variant names:

• chr17-19743244-C-G
• NM_000691.5:c.382G>C

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_000691.5(ALDH3A1):​c.382G>C​(p.Ala128Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ALDH3A1 NM_000691.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.90

Genes affected

ALDH3A1 (HGNC:405): (aldehyde dehydrogenase 3 family member A1) Aldehyde dehydrogenases oxidize various aldehydes to the corresponding acids. They are involved in the detoxification of alcohol-derived acetaldehyde and in the metabolism of corticosteroids, biogenic amines, neurotransmitters, and lipid peroxidation. The enzyme encoded by this gene forms a cytoplasmic homodimer that preferentially oxidizes aromatic and medium-chain (6 carbons or more) saturated and unsaturated aldehyde substrates. It is thought to promote resistance to UV and 4-hydroxy-2-nonenal-induced oxidative damage in the cornea. The gene is located within the Smith-Magenis syndrome region on chromosome 17. Multiple alternatively spliced variants, encoding the same protein, have been identified. [provided by RefSeq, Sep 2008]

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.981

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALDH3A1	NM_000691.5	c.382G>C	p.Ala128Pro	missense_variant	Exon 3 of 11	ENST00000225740.11	NP_000682.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALDH3A1	ENST00000225740.11	c.382G>C	p.Ala128Pro	missense_variant	Exon 3 of 11	1	NM_000691.5	ENSP00000225740.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.92
BayesDel_addAF	Pathogenic	0.45	D
BayesDel_noAF	Pathogenic	0.41
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.60	.;D;D;D;D;D;D;D
Eigen	Pathogenic	0.69
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Pathogenic	0.99	D;D;.;D;.;D;D;D
M_CAP	Pathogenic	0.29	D
MetaRNN	Pathogenic	0.98	D;D;D;D;D;D;D;D
MetaSVM	Uncertain	0.45	D
MutationAssessor	Pathogenic	4.3	.;.;H;H;H;.;.;.
PrimateAI	Uncertain	0.57	T
PROVEAN	Pathogenic	-4.7	D;.;D;D;D;D;.;.
REVEL	Pathogenic	0.75
Sift	Pathogenic	0.0	D;.;D;D;D;D;.;.
Sift4G	Uncertain	0.0020	D;D;D;D;D;D;D;.
Polyphen		1.0	.;.;D;D;D;.;.;.
Vest4		0.90
MutPred		0.90		Gain of catalytic residue at G127 (P = 0.1791);.;Gain of catalytic residue at G127 (P = 0.1791);Gain of catalytic residue at G127 (P = 0.1791);Gain of catalytic residue at G127 (P = 0.1791);Gain of catalytic residue at G127 (P = 0.1791);.;Gain of catalytic residue at G127 (P = 0.1791);
MVP		0.96
MPC		0.92
ClinPred		0.99	D
GERP RS		2.8
Varity_R		0.98
gMVP		0.97

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-19646557;