Variant 17-19744989-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_000691.5(ALDH3A1):c.141G>A(p.Ala47=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0033 in 1,583,142 control chromosomes in the GnomAD database, including 72 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.012 ( 37 hom., cov: 32)

Exomes 𝑓: 0.0023 ( 35 hom. )

Consequence

ALDH3A1
NM_000691.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.220

Variant links:

Genes affected

ALDH3A1 (HGNC:405): (aldehyde dehydrogenase 3 family member A1) Aldehyde dehydrogenases oxidize various aldehydes to the corresponding acids. They are involved in the detoxification of alcohol-derived acetaldehyde and in the metabolism of corticosteroids, biogenic amines, neurotransmitters, and lipid peroxidation. The enzyme encoded by this gene forms a cytoplasmic homodimer that preferentially oxidizes aromatic and medium-chain (6 carbons or more) saturated and unsaturated aldehyde substrates. It is thought to promote resistance to UV and 4-hydroxy-2-nonenal-induced oxidative damage in the cornea. The gene is located within the Smith-Magenis syndrome region on chromosome 17. Multiple alternatively spliced variants, encoding the same protein, have been identified. [provided by RefSeq, Sep 2008]

ALDH3A1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.52).

BP6

Variant 17-19744989-C-T is Benign according to our data. Variant chr17-19744989-C-T is described in ClinVar as [Benign]. Clinvar id is 710461.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.22 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0124 (1882/151520) while in subpopulation AFR AF= 0.0384 (1584/41296). AF 95% confidence interval is 0.0368. There are 37 homozygotes in gnomad4. There are 872 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 37 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALDH3A1	NM_000691.5 linkuse as main transcript	c.141G>A	p.Ala47=	synonymous_variant	2/11	ENST00000225740.11	NP_000682.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALDH3A1	ENST00000225740.11 linkuse as main transcript	c.141G>A	p.Ala47=	synonymous_variant	2/11	1	NM_000691.5	ENSP00000225740	P1

Frequencies

GnomAD3 genomes

AF:

0.0124

AC:

1875

AN:

151404

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0383

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00960

Gnomad ASJ

AF:

0.0121

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000832

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00115

Gnomad OTH

AF:

0.0125

GnomAD3 exomes

AF:

0.00476

AC:

954

AN:

200506

Hom.:

AF XY:

0.00388

AC XY:

435

AN XY:

112174

show subpopulations

Gnomad AFR exome

AF:

0.0447

Gnomad AMR exome

AF:

0.00728

Gnomad ASJ exome

AF:

0.0114

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000637

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000950

Gnomad OTH exome

AF:

0.00750

GnomAD4 exome

AF:

0.00233

AC:

3335

AN:

1431622

Hom.:

Cov.:

AF XY:

0.00218

AC XY:

1553

AN XY:

711918

show subpopulations

Gnomad4 AFR exome

AF:

0.0408

Gnomad4 AMR exome

AF:

0.00715

Gnomad4 ASJ exome

AF:

0.0114

Gnomad4 EAS exome

AF:

0.0000261

Gnomad4 SAS exome

AF:

0.000615

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000896

Gnomad4 OTH exome

AF:

0.00536

GnomAD4 genome

AF:

0.0124

AC:

1882

AN:

151520

Hom.:

Cov.:

AF XY:

0.0118

AC XY:

872

AN XY:

73998

show subpopulations

Gnomad4 AFR

AF:

0.0384

Gnomad4 AMR

AF:

0.00959

Gnomad4 ASJ

AF:

0.0121

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000624

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00115

Gnomad4 OTH

AF:

0.0124

Alfa

AF:

0.00594

Hom.:

Bravo

AF:

0.0147

Asia WGS

AF:

0.00635

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Aug 04, 2018	- -
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

-0.52

CADD

Benign

DANN

Benign

0.82

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.13

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over