17-19742625-A-C

Variant names:

• chr17-19742625-A-C
• rs887241
• NM_000691.5:c.400T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000225740.11(ALDH3A1):​c.400T>G​(p.Ser134Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.675 in 1,613,612 control chromosomes in the GnomAD database, including 370,348 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.68 (35308 hom., cov: 33)
  • Exomes 𝑓: 0.67 (335040 hom.)
• Consequence: ALDH3A1 ENST00000225740.11 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.01
• Publications: 53 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=2.8962734E-6).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.924 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000225740.11. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALDH3A1	NM_000691.5	MANE Select	c.400T>G	p.Ser134Ala	missense	Exon 4 of 11	NP_000682.3
	ALDH3A1	NM_001135167.1		c.400T>G	p.Ser134Ala	missense	Exon 4 of 11	NP_001128639.1
	ALDH3A1	NM_001135168.1		c.400T>G	p.Ser134Ala	missense	Exon 3 of 10	NP_001128640.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALDH3A1	ENST00000225740.11	TSL:1 MANE Select	c.400T>G	p.Ser134Ala	missense	Exon 4 of 11	ENSP00000225740.6
	ALDH3A1	ENST00000457500.6	TSL:1	c.400T>G	p.Ser134Ala	missense	Exon 3 of 10	ENSP00000411821.2
	ALDH3A1	ENST00000444455.5	TSL:5	c.400T>G	p.Ser134Ala	missense	Exon 4 of 11	ENSP00000388469.1

Frequencies

GnomAD3 genomes AF: 0.679 AC: 103084 AN: 151928 Hom.: 35273 Cov.: 33

Gnomad AFR AF: 0.652

Gnomad AMI AF: 0.725

Gnomad AMR AF: 0.736

Gnomad ASJ AF: 0.596

Gnomad EAS AF: 0.946

Gnomad SAS AF: 0.753

Gnomad FIN AF: 0.656

Gnomad MID AF: 0.617

Gnomad NFE AF: 0.663

Gnomad OTH AF: 0.674

GnomAD2 exomes AF: 0.706 AC: 177235 AN: 251140 AF XY: 0.702

Gnomad AFR exome AF: 0.652

Gnomad AMR exome AF: 0.779

Gnomad ASJ exome AF: 0.602

Gnomad EAS exome AF: 0.947

Gnomad FIN exome AF: 0.661

Gnomad NFE exome AF: 0.664

Gnomad OTH exome AF: 0.664

GnomAD4 exome AF: 0.675 AC: 985853 AN: 1461566 Hom.: 335040 Cov.: 69 AF XY: 0.676 AC XY: 491422 AN XY: 727088

African (AFR) AF: 0.648 AC: 21697 AN: 33478

American (AMR) AF: 0.771 AC: 34498 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.604 AC: 15785 AN: 26132

East Asian (EAS) AF: 0.951 AC: 37765 AN: 39700

South Asian (SAS) AF: 0.734 AC: 63338 AN: 86258

European-Finnish (FIN) AF: 0.663 AC: 35233 AN: 53170

Middle Eastern (MID) AF: 0.555 AC: 3200 AN: 5768

European-Non Finnish (NFE) AF: 0.660 AC: 733921 AN: 1111950

Other (OTH) AF: 0.669 AC: 40416 AN: 60390

GnomAD4 genome AF: 0.679 AC: 103174 AN: 152046 Hom.: 35308 Cov.: 33 AF XY: 0.683 AC XY: 50732 AN XY: 74316

African (AFR) AF: 0.652 AC: 27048 AN: 41464

American (AMR) AF: 0.736 AC: 11257 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.596 AC: 2068 AN: 3472

East Asian (EAS) AF: 0.946 AC: 4884 AN: 5162

South Asian (SAS) AF: 0.753 AC: 3625 AN: 4812

European-Finnish (FIN) AF: 0.656 AC: 6942 AN: 10580

Middle Eastern (MID) AF: 0.616 AC: 181 AN: 294

European-Non Finnish (NFE) AF: 0.663 AC: 45078 AN: 67956

Other (OTH) AF: 0.678 AC: 1431 AN: 2110

Alfa AF: 0.670 Hom.: 157355

Bravo AF: 0.681

TwinsUK AF: 0.669 AC: 2482

ALSPAC AF: 0.649 AC: 2502

ESP6500AA AF: 0.643 AC: 2833

ESP6500EA AF: 0.659 AC: 5664

ExAC AF: 0.704 AC: 85457

Asia WGS AF: 0.849 AC: 2950 AN: 3478

EpiCase AF: 0.656

EpiControl AF: 0.651

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.051
BayesDel_addAF	Benign	-0.66	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	2.2
DANN	Benign	0.55
DEOGEN2	Benign	0.083	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.018	N
LIST_S2	Benign	0.43	T
MetaRNN	Benign	0.0000029	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	-0.92	N
PhyloP100		1.0
PrimateAI	Uncertain	0.48	T
PROVEAN	Benign	2.4	N
REVEL	Benign	0.18
Sift	Benign	0.69	T
Sift4G	Benign	0.50	T
Polyphen		0.0	B
Vest4		0.061
MPC		0.18
ClinPred		0.00030	T
GERP RS		3.6
Varity_R		0.075
gMVP		0.53
Mutation Taster		=95/5	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs887241; hg19: chr17-19645938; COSMIC: COSV56734903; COSMIC: COSV56734903;