17-19742209-G-T

Variant names:

• chr17-19742209-G-T
• rs747613567
• NM_000691.5:c.484C>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_000691.5(ALDH3A1):​c.484C>A​(p.Leu162Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L162V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ALDH3A1 NM_000691.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.993
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.41648287).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000691.5. 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
	ALDH3A1	NM_000691.5	MANE Select	c.484C>A	p.Leu162Met	missense	Exon 5 of 11	NP_000682.3
	ALDH3A1	NM_001135167.1		c.484C>A	p.Leu162Met	missense	Exon 5 of 11	NP_001128639.1	P30838
	ALDH3A1	NM_001135168.1		c.484C>A	p.Leu162Met	missense	Exon 4 of 10	NP_001128640.1	P30838

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALDH3A1	ENST00000225740.11	TSL:1 MANE Select	c.484C>A	p.Leu162Met	missense	Exon 5 of 11	ENSP00000225740.6	P30838
	ALDH3A1	ENST00000457500.6	TSL:1	c.484C>A	p.Leu162Met	missense	Exon 4 of 10	ENSP00000411821.2	P30838
	ALDH3A1	ENST00000905965.1		c.484C>A	p.Leu162Met	missense	Exon 5 of 11	ENSP00000576024.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.040	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.20	T
Eigen	Benign	0.048
Eigen_PC	Benign	-0.10
FATHMM_MKL	Benign	0.65	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.060	D
MetaRNN	Benign	0.42	T
MetaSVM	Uncertain	-0.16	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		0.99
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-0.82	N
REVEL	Uncertain	0.37
Sift	Benign	0.15	T
Sift4G	Benign	0.12	T
Polyphen		0.97	D
Vest4		0.36
MutPred		0.42		Gain of methylation at K160 (P = 0.0728)
MVP		0.77
MPC		0.42
ClinPred		0.87	D
GERP RS		0.97
Varity_R		0.55
gMVP		0.53

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

Other links and lift over

dbSNP: rs747613567; hg19: chr17-19645522;