17-19677181-A-G

Position:

• chr17-19677181-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000382.3(ALDH3A2):​c.*1609A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.518 in 152,104 control chromosomes in the GnomAD database, including 21,386 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.52 (21386 hom., cov: 33)
  • Exomes 𝑓: 0.50 (0 hom.)
• Consequence: ALDH3A2 NM_000382.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.21

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 17-19677181-A-G is Benign according to our data. Variant chr17-19677181-A-G is described in ClinVar as [Benign]. Clinvar id is 322237.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.886 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALDH3A2	NM_000382.3	c.*1609A>G		3_prime_UTR_variant	10/10	ENST00000176643.11	NP_000373.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALDH3A2	ENST00000176643.11	c.*1609A>G		3_prime_UTR_variant	10/10	1	NM_000382.3	ENSP00000176643.6

Frequencies

GnomAD3 genomes AF: 0.518 AC: 78656 AN: 151984 Hom.: 21360 Cov.: 33

Gnomad AFR AF: 0.385

Gnomad AMI AF: 0.603

Gnomad AMR AF: 0.646

Gnomad ASJ AF: 0.466

Gnomad EAS AF: 0.908

Gnomad SAS AF: 0.667

Gnomad FIN AF: 0.479

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.536

Gnomad OTH AF: 0.517

GnomAD4 exome AF: 0.500 AC: 1 AN: 2 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

Gnomad4 FIN exome AF: 0.500

GnomAD4 genome AF: 0.518 AC: 78729 AN: 152102 Hom.: 21386 Cov.: 33 AF XY: 0.524 AC XY: 38964 AN XY: 74332

Gnomad4 AFR AF: 0.386

Gnomad4 AMR AF: 0.646

Gnomad4 ASJ AF: 0.466

Gnomad4 EAS AF: 0.908

Gnomad4 SAS AF: 0.667

Gnomad4 FIN AF: 0.479

Gnomad4 NFE AF: 0.536

Gnomad4 OTH AF: 0.521

Alfa AF: 0.541 Hom.: 27145

Bravo AF: 0.522

Asia WGS AF: 0.780 AC: 2710 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Sjögren-Larsson syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.1
DANN	Benign	0.76

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: rs7215; hg19: chr17-19580494; COSMIC: COSV51568524; COSMIC: COSV51568524;