NM_000382.3:c.1443+452A>G

Variant names:

• chr17-19672408-A-G
• rs2072331
• NM_000382.3:c.1443+452A>G

Variant summary

Our verdict is Benign. The variant received -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
• 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: G2P, Myriad Women’s Health, PanelApp Australia, 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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.373 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.1443+452A>G		intron	N/A	NP_000373.1
	ALDH3A2	NM_001031806.2		c.1443+452A>G		intron	N/A	NP_001026976.1
	ALDH3A2	NM_001369136.1		c.1443+452A>G		intron	N/A	NP_001356065.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALDH3A2	ENST00000176643.11	TSL:1 MANE Select	c.1443+452A>G		intron	N/A	ENSP00000176643.6
	ALDH3A2	ENST00000339618.8	TSL:1	c.1443+452A>G		intron	N/A	ENSP00000345774.4
	ALDH3A2	ENST00000476965.5	TSL:1	n.1193+452A>G		intron	N/A

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

African (AFR) AF: 0.0719 AC: 80 AN: 1112

American (AMR) AF: 0.277 AC: 985 AN: 3562

Ashkenazi Jewish (ASJ) AF: 0.140 AC: 96 AN: 684

East Asian (EAS) AF: 0.370 AC: 999 AN: 2700

South Asian (SAS) AF: 0.192 AC: 830 AN: 4318

European-Finnish (FIN) AF: 0.192 AC: 214 AN: 1112

Middle Eastern (MID) AF: 0.0600 AC: 6 AN: 100

European-Non Finnish (NFE) AF: 0.219 AC: 4616 AN: 21120

Other (OTH) AF: 0.207 AC: 348 AN: 1684

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

African (AFR) AF: 0.0905 AC: 3757 AN: 41520

American (AMR) AF: 0.275 AC: 4204 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.153 AC: 530 AN: 3468

East Asian (EAS) AF: 0.387 AC: 1995 AN: 5156

South Asian (SAS) AF: 0.241 AC: 1159 AN: 4816

European-Finnish (FIN) AF: 0.210 AC: 2229 AN: 10602

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.245 AC: 16684 AN: 67990

Other (OTH) AF: 0.199 AC: 420 AN: 2110

Alfa AF: 0.230 Hom.: 8110

Bravo AF: 0.204

Asia WGS AF: 0.276 AC: 959 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.1
DANN	Benign	0.52
PhyloP100		0.15
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: rs2072331; hg19: chr17-19575721;