Variant chr17-19648972-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate

The NM_000382.3(ALDH3A2):c.1A>G(p.Met1?) variant causes a start lost change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000209 in 1,434,150 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

ALDH3A2
NM_000382.3 start_lost

Scores

Clinical Significance

Likely pathogenic criteria provided, single submitter P:1

Conservation

PhyloP100: 1.28

Variant links:

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 links:

ALDH3A2 (HGNC:):

ALDH3A2 links:

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ACMG classification

Classification made for transcript

Verdict is Pathogenic. Variant got 12 ACMG points.

PVS1

Start lost variant, no new inframe start found.

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant 17-19648972-A-G is Pathogenic according to our data. Variant chr17-19648972-A-G is described in ClinVar as [Likely_pathogenic]. Clinvar id is 551722.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALDH3A2	NM_000382.3 linkuse as main transcript	c.1A>G	p.Met1?	start_lost	1/10	ENST00000176643.11	NP_000373.1	P51648-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALDH3A2	ENST00000176643.11 linkuse as main transcript	c.1A>G	p.Met1?	start_lost	1/10	1	NM_000382.3	ENSP00000176643.6		P51648-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000209

AC:

AN:

1434150

Hom.:

Cov.:

AF XY:

0.00000281

AC XY:

AN XY:

710838

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000182

Gnomad4 OTH exome

AF:

0.0000169

GnomAD4 genome

Cov.:

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Sjögren-Larsson syndrome

Pathogenic:1

Likely pathogenic, criteria provided, single submitter

clinical testing

Counsyl

May 02, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.23

BayesDel_noAF

Uncertain

0.090

CADD

Uncertain

DANN

Benign

0.96

DEOGEN2

Benign

0.0097

.;T;.;.;T;.;T;.;T

Eigen

Uncertain

0.45

Eigen_PC

Uncertain

0.43

FATHMM_MKL

Uncertain

0.82

LIST_S2

Uncertain

0.90

D;D;.;.;D;.;.;D;.

M_CAP

Pathogenic

0.97

MetaRNN

Pathogenic

0.98

D;D;D;D;D;D;D;D;D

MetaSVM

Uncertain

0.28

MutationTaster

Benign

1.0

D;D;D;D;D

PROVEAN

Benign

-1.0

N;.;.;.;N;.;N;N;.

REVEL

Uncertain

0.62

Sift

Uncertain

0.023

D;.;.;.;D;.;D;D;.

Sift4G

Uncertain

0.030

D;D;D;T;D;T;D;T;D

Polyphen

0.97, 0.99

.;.;.;.;D;D;D;D;D

Vest4

0.40, 0.68, 0.68, 0.42, 0.68, 0.73, 0.67

MutPred

0.87

Gain of methylation at R6 (P = 0.1593);Gain of methylation at R6 (P = 0.1593);Gain of methylation at R6 (P = 0.1593);Gain of methylation at R6 (P = 0.1593);Gain of methylation at R6 (P = 0.1593);Gain of methylation at R6 (P = 0.1593);Gain of methylation at R6 (P = 0.1593);Gain of methylation at R6 (P = 0.1593);Gain of methylation at R6 (P = 0.1593);

MVP

0.90

ClinPred

0.99

GERP RS

5.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.83

gMVP

0.51

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over