Variant rs3743477 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_022767.4(AEN):c.44C>T(p.Pro15Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0543 in 1,611,698 control chromosomes in the GnomAD database, including 2,977 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.072 ( 505 hom., cov: 33)

Exomes 𝑓: 0.052 ( 2472 hom. )

Consequence

AEN
NM_022767.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.792

Variant links:

Genes affected

AEN (HGNC:25722): (apoptosis enhancing nuclease) Enables exonuclease activity. Involved in intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator and response to ionizing radiation. Located in nuclear membrane; nucleolus; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

AEN links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0014880002).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.121 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AEN	NM_022767.4 linkuse as main transcript	c.44C>T	p.Pro15Leu	missense_variant	2/4	ENST00000332810.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AEN	ENST00000332810.4 linkuse as main transcript	c.44C>T	p.Pro15Leu	missense_variant	2/4	1	NM_022767.4	P1	Q8WTP8-1
AEN	ENST00000557787.1 linkuse as main transcript	n.154C>T		non_coding_transcript_exon_variant	2/2	1
AEN	ENST00000559528.1 linkuse as main transcript	c.44C>T	p.Pro15Leu	missense_variant	2/2	2
AEN	ENST00000558327.1 linkuse as main transcript	n.525C>T		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes

AF:

0.0719

AC:

10952

AN:

152228

Hom.:

499

Cov.:

show subpopulations

Gnomad AFR

AF:

0.123

Gnomad AMI

AF:

0.0351

Gnomad AMR

AF:

0.0489

Gnomad ASJ

AF:

0.0616

Gnomad EAS

AF:

0.000961

Gnomad SAS

AF:

0.0928

Gnomad FIN

AF:

0.0664

Gnomad MID

AF:

0.114

Gnomad NFE

AF:

0.0518

Gnomad OTH

AF:

0.0640

GnomAD3 exomes

AF:

0.0582

AC:

14440

AN:

247938

Hom.:

575

AF XY:

0.0603

AC XY:

8103

AN XY:

134420

show subpopulations

Gnomad AFR exome

AF:

0.124

Gnomad AMR exome

AF:

0.0319

Gnomad ASJ exome

AF:

0.0636

Gnomad EAS exome

AF:

0.000656

Gnomad SAS exome

AF:

0.0979

Gnomad FIN exome

AF:

0.0758

Gnomad NFE exome

AF:

0.0515

Gnomad OTH exome

AF:

0.0651

GnomAD4 exome

AF:

0.0524

AC:

76512

AN:

1459352

Hom.:

2472

Cov.:

AF XY:

0.0542

AC XY:

39331

AN XY:

725796

show subpopulations

Gnomad4 AFR exome

AF:

0.125

Gnomad4 AMR exome

AF:

0.0342

Gnomad4 ASJ exome

AF:

0.0623

Gnomad4 EAS exome

AF:

0.00131

Gnomad4 SAS exome

AF:

0.0986

Gnomad4 FIN exome

AF:

0.0751

Gnomad4 NFE exome

AF:

0.0474

Gnomad4 OTH exome

AF:

0.0582

GnomAD4 genome

AF:

0.0721

AC:

10977

AN:

152346

Hom.:

505

Cov.:

AF XY:

0.0727

AC XY:

5419

AN XY:

74496

show subpopulations

Gnomad4 AFR

AF:

0.123

Gnomad4 AMR

AF:

0.0489

Gnomad4 ASJ

AF:

0.0616

Gnomad4 EAS

AF:

0.000963

Gnomad4 SAS

AF:

0.0914

Gnomad4 FIN

AF:

0.0664

Gnomad4 NFE

AF:

0.0518

Gnomad4 OTH

AF:

0.0681

Alfa

AF:

0.0524

Hom.:

515

Bravo

AF:

0.0704

TwinsUK

AF:

0.0518

AC:

192

ALSPAC

AF:

0.0451

AC:

174

ESP6500AA

AF:

0.116

AC:

509

ESP6500EA

AF:

0.0512

AC:

440

ExAC

AF:

0.0603

AC:

7319

Asia WGS

AF:

0.0640

AC:

222

AN:

3478

EpiCase

AF:

0.0509

EpiControl

AF:

0.0522

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.084

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.64

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.021

T;T

Eigen

Benign

-0.73

Eigen_PC

Benign

-0.73

FATHMM_MKL

Benign

0.24

LIST_S2

Benign

0.70

T;T

MetaRNN

Benign

0.0015

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.98

L;.

MutationTaster

Benign

1.0

P;P

PrimateAI

Benign

0.39

PROVEAN

Benign

0.26

N;N

REVEL

Benign

0.047

Sift

Uncertain

0.0050

D;D

Sift4G

Uncertain

0.0090

D;D

Polyphen

0.0010

B;.

Vest4

0.067

MPC

0.084

ClinPred

0.0054

GERP RS

2.3

Varity_R

0.079

gMVP

0.38

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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