17-19648739-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The ENST00000672357.1(ALDH3A2):c.-142T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00471 in 599,782 control chromosomes in the GnomAD database, including 65 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.013 (50 hom., cov: 33)
  • Exomes 𝑓: 0.0019 (15 hom.)
• Consequence: ALDH3A2 ENST00000672357.1 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.611

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 17-19648739-T-C is Benign according to our data. Variant chr17-19648739-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 1326534.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0129 (1963/152312) while in subpopulation AFR AF= 0.0438 (1823/41582). AF 95% confidence interval is 0.0422. There are 50 homozygotes in gnomad4. There are 945 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 49 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ALDH3A2	NM_000382.3			upstream_gene_variant		ENST00000176643.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ALDH3A2	ENST00000176643.11			upstream_gene_variant		1	NM_000382.3	P1

Frequencies

GnomAD3 genomes AF: 0.0129 AC: 1959 AN: 152196 Hom.: 49 Cov.: 33

Gnomad AFR AF: 0.0439

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00497

Gnomad ASJ AF: 0.00288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000441

Gnomad OTH AF: 0.00955

GnomAD4 exome AF: 0.00192 AC: 859 AN: 447470 Hom.: 15 Cov.: 5 AF XY: 0.00165 AC XY: 386 AN XY: 233780

Gnomad4 AFR exome AF: 0.0448

Gnomad4 AMR exome AF: 0.00343

Gnomad4 ASJ exome AF: 0.00262

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000869

Gnomad4 FIN exome AF: 0.0000356

Gnomad4 NFE exome AF: 0.000386

Gnomad4 OTH exome AF: 0.00356

GnomAD4 genome AF: 0.0129 AC: 1963 AN: 152312 Hom.: 50 Cov.: 33 AF XY: 0.0127 AC XY: 945 AN XY: 74476

Gnomad4 AFR AF: 0.0438

Gnomad4 AMR AF: 0.00496

Gnomad4 ASJ AF: 0.00288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000441

Gnomad4 OTH AF: 0.00945

Alfa AF: 0.00874 Hom.: 1

Bravo AF: 0.0143

Asia WGS AF: 0.00260 AC: 9 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

May 28, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	1.9
Dann	Benign	0.63

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: rs114897153; hg19: chr17-19552052;