rs2072331

Positions:

• chr17-19672408-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000382.3(ALDH3A2):​c.1443+452A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.209 in 188,550 control chromosomes in the GnomAD database, including 4,747 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 0.21 (3648 hom., cov: 32)
  • Exomes 𝑓: 0.22 (1099 hom.)
• Consequence: ALDH3A2 NM_000382.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.153

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.373 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALDH3A2	NM_000382.3	c.1443+452A>G		intron_variant		ENST00000176643.11	NP_000373.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALDH3A2	ENST00000176643.11	c.1443+452A>G		intron_variant		1	NM_000382.3	ENSP00000176643	P1

Frequencies

GnomAD3 genomes AF: 0.205 AC: 31202 AN: 152040 Hom.: 3643 Cov.: 32

Gnomad AFR AF: 0.0905

Gnomad AMI AF: 0.248

Gnomad AMR AF: 0.274

Gnomad ASJ AF: 0.153

Gnomad EAS AF: 0.387

Gnomad SAS AF: 0.241

Gnomad FIN AF: 0.210

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.245

Gnomad OTH AF: 0.196

GnomAD4 exome AF: 0.225 AC: 8174 AN: 36392 Hom.: 1099 Cov.: 0 AF XY: 0.220 AC XY: 4114 AN XY: 18674

Gnomad4 AFR exome AF: 0.0719

Gnomad4 AMR exome AF: 0.277

Gnomad4 ASJ exome AF: 0.140

Gnomad4 EAS exome AF: 0.370

Gnomad4 SAS exome AF: 0.192

Gnomad4 FIN exome AF: 0.192

Gnomad4 NFE exome AF: 0.219

Gnomad4 OTH exome AF: 0.207

GnomAD4 genome AF: 0.205 AC: 31232 AN: 152158 Hom.: 3648 Cov.: 32 AF XY: 0.207 AC XY: 15387 AN XY: 74384

Gnomad4 AFR AF: 0.0905

Gnomad4 AMR AF: 0.275

Gnomad4 ASJ AF: 0.153

Gnomad4 EAS AF: 0.387

Gnomad4 SAS AF: 0.241

Gnomad4 FIN AF: 0.210

Gnomad4 NFE AF: 0.245

Gnomad4 OTH AF: 0.199

Alfa AF: 0.233 Hom.: 5980

Bravo AF: 0.204

Asia WGS AF: 0.276 AC: 959 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.1
DANN	Benign	0.52

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

Publications

LitVar

Other links and lift over

dbSNP: rs2072331; hg19: chr17-19575721;