17-19648823-C-G

Position:

• chr17-19648823-C-G

Variant summary

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

The NM_000382.3(ALDH3A2):​c.-149C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00504 in 1,126,314 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0040 (1 hom., cov: 33)
  • Exomes 𝑓: 0.0052 (15 hom.)
• Consequence: ALDH3A2 NM_000382.3 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -4.72

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=-0.79).
• BP6: Variant 17-19648823-C-G is Benign according to our data. Variant chr17-19648823-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 322204.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00402 (613/152330) while in subpopulation NFE AF= 0.00711 (484/68040). AF 95% confidence interval is 0.00659. There are 1 homozygotes in gnomad4. There are 278 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome4 at 15 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ALDH3A2	NM_000382.3	c.-149C>G		5_prime_UTR_variant	1/10	ENST00000176643.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ALDH3A2	ENST00000176643.11	c.-149C>G		5_prime_UTR_variant	1/10	1	NM_000382.3	P1

Frequencies

GnomAD3 genomes AF: 0.00401 AC: 611 AN: 152212 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00140

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.00124

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00311

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00711

Gnomad OTH AF: 0.00191

GnomAD4 exome AF: 0.00520 AC: 5065 AN: 973984 Hom.: 15 Cov.: 13 AF XY: 0.00507 AC XY: 2461 AN XY: 485766

Gnomad4 AFR exome AF: 0.000810

Gnomad4 AMR exome AF: 0.000694

Gnomad4 ASJ exome AF: 0.00133

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000504

Gnomad4 FIN exome AF: 0.00473

Gnomad4 NFE exome AF: 0.00641

Gnomad4 OTH exome AF: 0.00384

GnomAD4 genome AF: 0.00402 AC: 613 AN: 152330 Hom.: 1 Cov.: 33 AF XY: 0.00373 AC XY: 278 AN XY: 74492

Gnomad4 AFR AF: 0.00139

Gnomad4 AMR AF: 0.00124

Gnomad4 ASJ AF: 0.00202

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00311

Gnomad4 NFE AF: 0.00711

Gnomad4 OTH AF: 0.00189

Alfa AF: 0.00603 Hom.: 1

Bravo AF: 0.00357

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Sjögren-Larsson syndrome Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.59
DANN	Benign	0.53
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs557068998; hg19: chr17-19552136;