NM_000382.3:c.-154G>A

Variant names:

• chr17-19648818-G-A
• rs562399103
• NM_000382.3:c.-154G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_000382.3(ALDH3A2):​c.-154G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000943 in 1,070,602 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0014 (2 hom., cov: 33)
  • Exomes 𝑓: 0.00087 (9 hom.)
• Consequence: ALDH3A2 NM_000382.3 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.27
• Publications: 0 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 17-19648818-G-A is Benign according to our data. Variant chr17-19648818-G-A is described in ClinVar as Benign. ClinVar VariationId is 322203.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.00136 (207/152352) while in subpopulation EAS AF = 0.0306 (158/5168). AF 95% confidence interval is 0.0267. There are 2 homozygotes in GnomAd4. There are 111 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

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.-154G>A		5_prime_UTR	Exon 1 of 10	NP_000373.1	P51648-1
	ALDH3A2	NM_001031806.2		c.-154G>A		5_prime_UTR	Exon 1 of 11	NP_001026976.1	P51648-2
	ALDH3A2	NM_001369136.1		c.-63G>A		5_prime_UTR	Exon 1 of 12	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.-154G>A		5_prime_UTR	Exon 1 of 10	ENSP00000176643.6	P51648-1
	ALDH3A2	ENST00000339618.8	TSL:1	c.-154G>A		5_prime_UTR	Exon 1 of 11	ENSP00000345774.4	P51648-2
	ALDH3A2	ENST00000671878.1		c.-154G>A		5_prime_UTR	Exon 1 of 10	ENSP00000500516.1	A0A5F9ZHN9

Frequencies

GnomAD3 genomes AF: 0.00135 AC: 206 AN: 152234 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.000362

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000392

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0303

Gnomad SAS AF: 0.00352

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.00191

GnomAD4 exome AF: 0.000874 AC: 803 AN: 918250 Hom.: 9 Cov.: 12 AF XY: 0.000906 AC XY: 416 AN XY: 458946

African (AFR) AF: 0.000135 AC: 3 AN: 22280

American (AMR) AF: 0.000215 AC: 6 AN: 27848

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18568

East Asian (EAS) AF: 0.0176 AC: 581 AN: 32948

South Asian (SAS) AF: 0.00158 AC: 96 AN: 60874

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 31198

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3014

European-Non Finnish (NFE) AF: 0.0000206 AC: 14 AN: 679612

Other (OTH) AF: 0.00246 AC: 103 AN: 41908

GnomAD4 genome AF: 0.00136 AC: 207 AN: 152352 Hom.: 2 Cov.: 33 AF XY: 0.00149 AC XY: 111 AN XY: 74510

African (AFR) AF: 0.000361 AC: 15 AN: 41592

American (AMR) AF: 0.000392 AC: 6 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.0306 AC: 158 AN: 5168

South Asian (SAS) AF: 0.00352 AC: 17 AN: 4830

European-Finnish (FIN) AF: 0.0000941 AC: 1 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000882 AC: 6 AN: 68032

Other (OTH) AF: 0.00189 AC: 4 AN: 2116

Alfa AF: 0.00124 Hom.: 0

Bravo AF: 0.00128

Asia WGS AF: 0.0150 AC: 52 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	Sjögren-Larsson syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.3
DANN	Benign	0.65
PhyloP100		1.3
PromoterAI		-0.067	Neutral
Mutation Taster		=300/0	polymorphism

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: rs562399103; hg19: chr17-19552131; COSMIC: COSV99450016; COSMIC: COSV99450016;