17-19648599-G-C

Variant summary

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

The ENST00000631291.2(ALDH3A2):c.-373G>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 0.00303 in 244,030 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0026 (3 hom., cov: 33)
  • Exomes 𝑓: 0.0038 (2 hom.)
• Consequence: ALDH3A2 ENST00000631291.2 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.90

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=-0.8).
• BP6: Variant 17-19648599-G-C is Benign according to our data. Variant chr17-19648599-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 1343035.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00255 (389/152280) while in subpopulation NFE AF= 0.00371 (252/68010). AF 95% confidence interval is 0.00333. There are 3 homozygotes in gnomad4. There are 186 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ALDH3A2	NM_001369137.2	c.-38+334G>C		intron_variant
ALDH3A2	NM_001369138.2	c.-38+334G>C		intron_variant
ALDH3A2	NM_001369146.2	c.-38+334G>C		intron_variant
ALDH3A2	NM_001369148.2	c.-726+334G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ALDH3A2	ENST00000626500.2	c.-373G>C		5_prime_UTR_variant	1/4	5
ALDH3A2	ENST00000631291.2	c.-373G>C		5_prime_UTR_variant	1/9	5
ALDH3A2	ENST00000580550.5	c.-10+334G>C		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.00256 AC: 389 AN: 152162 Hom.: 3 Cov.: 33

Gnomad AFR AF: 0.000145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0110

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00370

Gnomad OTH AF: 0.00143

GnomAD4 exome AF: 0.00381 AC: 350 AN: 91750 Hom.: 2 Cov.: 0 AF XY: 0.00346 AC XY: 169 AN XY: 48870

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000296

Gnomad4 ASJ exome AF: 0.000404

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0110

Gnomad4 NFE exome AF: 0.00476

Gnomad4 OTH exome AF: 0.00322

GnomAD4 genome AF: 0.00255 AC: 389 AN: 152280 Hom.: 3 Cov.: 33 AF XY: 0.00250 AC XY: 186 AN XY: 74460

Gnomad4 AFR AF: 0.000144

Gnomad4 AMR AF: 0.000261

Gnomad4 ASJ AF: 0.00202

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0110

Gnomad4 NFE AF: 0.00371

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.00350 Hom.: 0

Bravo AF: 0.00145

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

Apr 09, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	4.5
Dann	Benign	0.55

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: rs571225645; hg19: chr17-19551912;