17-19658116-T-G

Variant names:

• chr17-19658116-T-G
• rs4646800
• NM_000382.3:c.798+254T>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000382.3(ALDH3A2):​c.798+254T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.312 in 152,040 control chromosomes in the GnomAD database, including 7,612 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.31 (7612 hom., cov: 32)
• Consequence: ALDH3A2 NM_000382.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.540
• Publications: 5 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: G2P, Myriad Women’s Health, PanelApp Australia, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 17-19658116-T-G is Benign according to our data. Variant chr17-19658116-T-G is described in ClinVar as Benign. ClinVar VariationId is 1264127.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.505 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALDH3A2	NM_000382.3	c.798+254T>G		intron_variant	Intron 5 of 9	ENST00000176643.11	NP_000373.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALDH3A2	ENST00000176643.11	c.798+254T>G		intron_variant	Intron 5 of 9	1	NM_000382.3	ENSP00000176643.6

Frequencies

GnomAD3 genomes AF: 0.312 AC: 47382 AN: 151920 Hom.: 7607 Cov.: 32

Gnomad AFR AF: 0.295

Gnomad AMI AF: 0.353

Gnomad AMR AF: 0.371

Gnomad ASJ AF: 0.313

Gnomad EAS AF: 0.521

Gnomad SAS AF: 0.426

Gnomad FIN AF: 0.269

Gnomad MID AF: 0.396

Gnomad NFE AF: 0.291

Gnomad OTH AF: 0.320

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.312 AC: 47425 AN: 152040 Hom.: 7612 Cov.: 32 AF XY: 0.317 AC XY: 23537 AN XY: 74302

African (AFR) AF: 0.295 AC: 12234 AN: 41472

American (AMR) AF: 0.370 AC: 5656 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.313 AC: 1085 AN: 3464

East Asian (EAS) AF: 0.521 AC: 2685 AN: 5154

South Asian (SAS) AF: 0.426 AC: 2049 AN: 4810

European-Finnish (FIN) AF: 0.269 AC: 2846 AN: 10574

Middle Eastern (MID) AF: 0.391 AC: 115 AN: 294

European-Non Finnish (NFE) AF: 0.291 AC: 19756 AN: 67984

Other (OTH) AF: 0.322 AC: 678 AN: 2106

Alfa AF: 0.287 Hom.: 821

Bravo AF: 0.318

Asia WGS AF: 0.503 AC: 1751 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Nov 10, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.6
DANN	Benign	0.40
PhyloP100		0.54
Mutation Taster		=100/0	polymorphism (auto)

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: rs4646800; hg19: chr17-19561429;