Variant chr15-100879933-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_000693.4(ALDH1A3):c.26A>T(p.Glu9Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000995 in 1,467,676 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000040 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00011 ( 0 hom. )

Consequence

ALDH1A3
NM_000693.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.69

Variant links:

Genes affected

ALDH1A3 (HGNC:409): (aldehyde dehydrogenase 1 family member A3) This gene encodes an aldehyde dehydrogenase enzyme that uses retinal as a substrate. Mutations in this gene have been associated with microphthalmia, isolated 8, and expression changes have also been detected in tumor cells. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2014]

ALDH1A3 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.21229681).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALDH1A3	NM_000693.4 linkuse as main transcript	c.26A>T	p.Glu9Val	missense_variant	1/13	ENST00000329841.10	NP_000684.2
ALDH1A3	NM_001293815.2 linkuse as main transcript	c.26A>T	p.Glu9Val	missense_variant	1/10		NP_001280744.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALDH1A3	ENST00000329841.10 linkuse as main transcript	c.26A>T	p.Glu9Val	missense_variant	1/13	1	NM_000693.4	ENSP00000332256	P1

Frequencies

GnomAD3 genomes

AF:

0.0000395

AC:

AN:

151754

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000884

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000121

AC:

AN:

82642

Hom.:

AF XY:

0.0000214

AC XY:

AN XY:

46634

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000354

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000106

AC:

140

AN:

1315922

Hom.:

Cov.:

AF XY:

0.000113

AC XY:

AN XY:

648140

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:

0.000133

Gnomad4 OTH exome

AF:

0.0000371

GnomAD4 genome

AF:

0.0000395

AC:

AN:

151754

Hom.:

Cov.:

AF XY:

0.0000674

AC XY:

AN XY:

74144

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000884

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000302

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 08, 2023

The c.26A>T (p.E9V) alteration is located in exon 1 (coding exon 1) of the ALDH1A3 gene. This alteration results from a A to T substitution at nucleotide position 26, causing the glutamic acid (E) at amino acid position 9 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.025

BayesDel_noAF

Benign

-0.17

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.26

T;T;T

Eigen

Benign

-0.34

Eigen_PC

Benign

-0.20

FATHMM_MKL

Benign

0.73

LIST_S2

Benign

0.75

T;T;T

M_CAP

Pathogenic

0.55

MetaRNN

Benign

0.21

T;T;T

MetaSVM

Benign

-0.85

MutationAssessor

Benign

1.1

L;.;.

MutationTaster

Benign

1.0

D;D;N

PrimateAI

Uncertain

0.75

PROVEAN

Benign

-0.25

N;D;N

REVEL

Benign

0.27

Sift

Benign

0.066

T;D;D

Sift4G

Benign

0.14

T;D;T

Polyphen

0.0030

B;.;.

Vest4

0.43

MutPred

0.27

Loss of disorder (P = 0.0406);Loss of disorder (P = 0.0406);Loss of disorder (P = 0.0406);

MVP

0.66

MPC

0.65

ClinPred

0.23

GERP RS

2.7

Varity_R

0.19

gMVP

0.69

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

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