Variant NM_001040177.3:c.103G>A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 2P and 20B. PM1BP4_StrongBP6_Very_StrongBA1

The NM_001040177.3(AKR1E2):c.103G>A(p.Asp35Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0629 in 1,613,988 control chromosomes in the GnomAD database, including 3,594 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.052 ( 262 hom., cov: 32)

Exomes 𝑓: 0.064 ( 3332 hom. )

Consequence

AKR1E2
NM_001040177.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 7.41

Variant links:

Genes affected

AKR1E2 (HGNC:23437): (aldo-keto reductase family 1 member E2) The protein encoded by this gene is a member of the aldo-keto reductase superfamily. Members in this family are characterized by their structure (evolutionarily highly conserved TIM barrel) and function (NAD(P)H-dependent oxido-reduction of carbonyl groups). Transcripts of this gene have been reported in specimens of human testis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2012]

AKR1E2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 ACMG points.

PM1

In a binding_site (size 0) in uniprot entity AKCL2_HUMAN

BP4

Computational evidence support a benign effect (MetaRNN=0.004357338).

BP6

Variant 10-4830738-G-A is Benign according to our data. Variant chr10-4830738-G-A is described in ClinVar as [Benign]. Clinvar id is 677203.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0671 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AKR1E2	NM_001040177.3 link	c.103G>A	p.Asp35Asn	missense_variant	Exon 2 of 10	ENST00000298375.12	NP_001035267.1	Q96JD6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AKR1E2	ENST00000298375.12 link	c.103G>A	p.Asp35Asn	missense_variant	Exon 2 of 10	1	NM_001040177.3	ENSP00000298375.7		Q96JD6-1

Frequencies

GnomAD3 genomes

AF:

0.0519

AC:

7896

AN:

152058

Hom.:

262

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0333

Gnomad AMI

AF:

0.162

Gnomad AMR

AF:

0.0309

Gnomad ASJ

AF:

0.0383

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0238

Gnomad FIN

AF:

0.0815

Gnomad MID

AF:

0.0475

Gnomad NFE

AF:

0.0688

Gnomad OTH

AF:

0.0450

GnomAD3 exomes

AF:

0.0518

AC:

13035

AN:

251466

Hom.:

434

AF XY:

0.0514

AC XY:

6987

AN XY:

135910

show subpopulations

Gnomad AFR exome

AF:

0.0346

Gnomad AMR exome

AF:

0.0253

Gnomad ASJ exome

AF:

0.0391

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0271

Gnomad FIN exome

AF:

0.0888

Gnomad NFE exome

AF:

0.0715

Gnomad OTH exome

AF:

0.0526

GnomAD4 exome

AF:

0.0641

AC:

93653

AN:

1461812

Hom.:

3332

Cov.:

AF XY:

0.0629

AC XY:

45751

AN XY:

727206

show subpopulations

Gnomad4 AFR exome

AF:

0.0372

Gnomad4 AMR exome

AF:

0.0266

Gnomad4 ASJ exome

AF:

0.0393

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0265

Gnomad4 FIN exome

AF:

0.0895

Gnomad4 NFE exome

AF:

0.0715

Gnomad4 OTH exome

AF:

0.0568

GnomAD4 genome

AF:

0.0519

AC:

7900

AN:

152176

Hom.:

262

Cov.:

AF XY:

0.0508

AC XY:

3781

AN XY:

74400

show subpopulations

Gnomad4 AFR

AF:

0.0333

Gnomad4 AMR

AF:

0.0309

Gnomad4 ASJ

AF:

0.0383

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.0239

Gnomad4 FIN

AF:

0.0815

Gnomad4 NFE

AF:

0.0688

Gnomad4 OTH

AF:

0.0445

Alfa

AF:

0.0622

Hom.:

491

Bravo

AF:

0.0488

TwinsUK

AF:

0.0696

AC:

258

ALSPAC

AF:

0.0623

AC:

240

ESP6500AA

AF:

0.0354

AC:

156

ESP6500EA

AF:

0.0658

AC:

566

ExAC

AF:

0.0544

AC:

6604

Asia WGS

AF:

0.0130

AC:

AN:

3478

EpiCase

AF:

0.0609

EpiControl

AF:

0.0655

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 17, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.50

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.25

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.17

T;T;.;.;.

Eigen

Benign

-0.070

Eigen_PC

Benign

-0.15

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.91

D;D;D;D;D

MetaRNN

Benign

0.0044

T;T;T;T;T

MetaSVM

Uncertain

-0.26

MutationAssessor

Pathogenic

4.1

.;H;H;H;H

PrimateAI

Benign

0.42

PROVEAN

Pathogenic

-4.5

D;D;D;D;D

REVEL

Uncertain

0.36

Sift

Uncertain

0.010

D;D;D;D;D

Sift4G

Uncertain

0.017

D;D;D;D;D

Polyphen

0.090, 0.67, 0.57, 0.28

.;B;P;P;B

Vest4

0.25, 0.15, 0.24, 0.18

MPC

0.16

ClinPred

0.10

GERP RS

3.0

Varity_R

0.62

gMVP

0.92

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