rs962801

Variant names:

• chr17-19655782-C-T
• rs962801
• NM_000382.3:c.472-584C>T

Variant summary

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

The NM_000382.3(ALDH3A2):​c.472-584C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.278 in 152,214 control chromosomes in the GnomAD database, including 6,342 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.28 (6342 hom., cov: 33)
• Consequence: ALDH3A2 NM_000382.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.14
• Publications: 13 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 syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Myriad Women’s Health, G2P, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.505 is higher than 0.05.

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	NM_000382.3	MANE Select	c.472-584C>T		intron	N/A	NP_000373.1	P51648-1
	ALDH3A2	NM_001031806.2		c.472-584C>T		intron	N/A	NP_001026976.1	P51648-2
	ALDH3A2	NM_001369136.1		c.472-584C>T		intron	N/A	NP_001356065.1	P51648-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALDH3A2	ENST00000176643.11	TSL:1 MANE Select	c.472-584C>T		intron	N/A	ENSP00000176643.6	P51648-1
	ALDH3A2	ENST00000339618.8	TSL:1	c.472-584C>T		intron	N/A	ENSP00000345774.4	P51648-2
	ALDH3A2	ENST00000671878.1		c.472-584C>T		intron	N/A	ENSP00000500516.1	A0A5F9ZHN9

Frequencies

GnomAD3 genomes AF: 0.278 AC: 42291 AN: 152096 Hom.: 6347 Cov.: 33

Gnomad AFR AF: 0.183

Gnomad AMI AF: 0.353

Gnomad AMR AF: 0.348

Gnomad ASJ AF: 0.312

Gnomad EAS AF: 0.521

Gnomad SAS AF: 0.425

Gnomad FIN AF: 0.270

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.289

Gnomad OTH AF: 0.285

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.278 AC: 42299 AN: 152214 Hom.: 6342 Cov.: 33 AF XY: 0.283 AC XY: 21081 AN XY: 74416

African (AFR) AF: 0.183 AC: 7608 AN: 41546

American (AMR) AF: 0.348 AC: 5315 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.312 AC: 1084 AN: 3472

East Asian (EAS) AF: 0.521 AC: 2694 AN: 5170

South Asian (SAS) AF: 0.425 AC: 2053 AN: 4826

European-Finnish (FIN) AF: 0.270 AC: 2858 AN: 10588

Middle Eastern (MID) AF: 0.367 AC: 108 AN: 294

European-Non Finnish (NFE) AF: 0.289 AC: 19651 AN: 68006

Other (OTH) AF: 0.287 AC: 606 AN: 2110

Alfa AF: 0.295 Hom.: 11628

Bravo AF: 0.278

Asia WGS AF: 0.494 AC: 1719 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.13
DANN	Benign	0.59
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs962801; hg19: chr17-19559095; COSMIC: COSV51568421; COSMIC: COSV51568421;