Variant chr1-19312033-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_003689.4(AKR7A2):c.92C>A(p.Ser31Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.000027 in 1,408,820 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 0.00013 ( 0 hom., cov: 34)

Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

AKR7A2
NM_003689.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.72

Variant links:

Genes affected

AKR7A2 (HGNC:389): (aldo-keto reductase family 7 member A2) The protein encoded by this gene belongs to the aldo/keto reductase (AKR) superfamily and AKR7 family, which are involved in the detoxification of aldehydes and ketones. The AKR7 family consists of 3 genes that are present in a cluster on the p arm of chromosome 1. This protein, thought to be localized in the golgi, catalyzes the NADPH-dependent reduction of succinic semialdehyde to the endogenous neuromodulator, gamma-hydroxybutyrate. It may also function as a detoxication enzyme in the reduction of aflatoxin B1 and 2-carboxybenzaldehyde. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2016]

AKR7A2 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.008188546).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
AKR7A2	NM_003689.4 linkuse as main transcript	c.92C>A	p.Ser31Tyr	missense_variant	1/7	ENST00000235835.8
AKR7A2	NM_001320979.1 linkuse as main transcript	c.92C>A	p.Ser31Tyr	missense_variant	1/6
AKR7A2	XM_047433095.1 linkuse as main transcript	c.92C>A	p.Ser31Tyr	missense_variant	1/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
AKR7A2	ENST00000235835.8 linkuse as main transcript	c.92C>A	p.Ser31Tyr	missense_variant	1/7	1	NM_003689.4	P1
AKR7A2	ENST00000330072.9 linkuse as main transcript	c.62C>A	p.Ser21Tyr	missense_variant	1/6	2
AKR7A2	ENST00000492217.1 linkuse as main transcript	n.71C>A		non_coding_transcript_exon_variant	1/3	2

Frequencies

GnomAD3 genomes

AF:

0.000132

AC:

AN:

151986

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000483

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000273

AC:

AN:

36588

Hom.:

AF XY:

0.00

AC XY:

AN XY:

22130

show subpopulations

Gnomad AFR exome

AF:

0.00192

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000143

AC:

AN:

1256834

Hom.:

Cov.:

AF XY:

0.00000973

AC XY:

AN XY:

616520

show subpopulations

Gnomad4 AFR exome

AF:

0.000736

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.000132

AC:

AN:

151986

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

74230

show subpopulations

Gnomad4 AFR

AF:

0.000483

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:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.000185

ExAC

AF:

0.0000597

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Benign

0.86

DEOGEN2

Benign

0.0051

T;.

Eigen

Benign

-0.69

Eigen_PC

Benign

-0.76

FATHMM_MKL

Benign

0.65

LIST_S2

Benign

0.50

T;T

M_CAP

Pathogenic

0.42

MetaRNN

Benign

0.0082

T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.0

N;.

MutationTaster

Benign

0.96

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

-2.4

N;N

REVEL

Benign

0.13

Sift

Uncertain

0.010

D;D

Sift4G

Uncertain

0.011

D;D

Polyphen

0.23

B;.

Vest4

0.33

MutPred

0.36

Loss of glycosylation at S31 (P = 0.0111);.;

MVP

0.44

MPC

2.1

ClinPred

0.20

GERP RS

2.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.094

gMVP

0.25

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over