Variant rs10999147 details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_032797.6(AIFM2):c.404T>C(p.Met135Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0815 in 1,612,740 control chromosomes in the GnomAD database, including 6,278 homozygotes. In-silico tool predicts 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 0.065 ( 459 hom., cov: 28)

Exomes 𝑓: 0.083 ( 5819 hom. )

Consequence

AIFM2
NM_032797.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.88

Variant links:

Genes affected

AIFM2 (HGNC:21411): (apoptosis inducing factor mitochondria associated 2) This gene encodes a flavoprotein oxidoreductase that binds single stranded DNA and is thought to contribute to apoptosis in the presence of bacterial and viral DNA. The expression of this gene is also found to be induced by tumor suppressor protein p53 in colon cancer cells. [provided by RefSeq, Nov 2010]

AIFM2 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=0.0016267002).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.142 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AIFM2	NM_032797.6 linkuse as main transcript	c.404T>C	p.Met135Thr	missense_variant	4/9	ENST00000307864.3	NP_116186.1
AIFM2	NM_001198696.2 linkuse as main transcript	c.404T>C	p.Met135Thr	missense_variant	4/9		NP_001185625.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AIFM2	ENST00000307864.3 linkuse as main transcript	c.404T>C	p.Met135Thr	missense_variant	4/9	1	NM_032797.6	ENSP00000312370	P1	Q9BRQ8-1
AIFM2	ENST00000373248.5 linkuse as main transcript	c.404T>C	p.Met135Thr	missense_variant	3/9	1		ENSP00000362345	P1	Q9BRQ8-1
AIFM2	ENST00000613322.4 linkuse as main transcript	c.404T>C	p.Met135Thr	missense_variant	4/9	5		ENSP00000478931	P1	Q9BRQ8-1

Frequencies

GnomAD3 genomes

AF:

0.0645

AC:

9797

AN:

151784

Hom.:

458

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0214

Gnomad AMI

AF:

0.0296

Gnomad AMR

AF:

0.0627

Gnomad ASJ

AF:

0.169

Gnomad EAS

AF:

0.135

Gnomad SAS

AF:

0.151

Gnomad FIN

AF:

0.0383

Gnomad MID

AF:

0.152

Gnomad NFE

AF:

0.0778

Gnomad OTH

AF:

0.0866

GnomAD3 exomes

AF:

0.0861

AC:

21546

AN:

250222

Hom.:

1191

AF XY:

0.0927

AC XY:

12545

AN XY:

135296

show subpopulations

Gnomad AFR exome

AF:

0.0210

Gnomad AMR exome

AF:

0.0442

Gnomad ASJ exome

AF:

0.159

Gnomad EAS exome

AF:

0.137

Gnomad SAS exome

AF:

0.156

Gnomad FIN exome

AF:

0.0430

Gnomad NFE exome

AF:

0.0823

Gnomad OTH exome

AF:

0.0941

GnomAD4 exome

AF:

0.0833

AC:

121688

AN:

1460838

Hom.:

5819

Cov.:

AF XY:

0.0859

AC XY:

62419

AN XY:

726744

show subpopulations

Gnomad4 AFR exome

AF:

0.0222

Gnomad4 AMR exome

AF:

0.0464

Gnomad4 ASJ exome

AF:

0.161

Gnomad4 EAS exome

AF:

0.142

Gnomad4 SAS exome

AF:

0.154

Gnomad4 FIN exome

AF:

0.0432

Gnomad4 NFE exome

AF:

0.0779

Gnomad4 OTH exome

AF:

0.0949

GnomAD4 genome

AF:

0.0645

AC:

9802

AN:

151902

Hom.:

459

Cov.:

AF XY:

0.0648

AC XY:

4813

AN XY:

74244

show subpopulations

Gnomad4 AFR

AF:

0.0214

Gnomad4 AMR

AF:

0.0626

Gnomad4 ASJ

AF:

0.169

Gnomad4 EAS

AF:

0.135

Gnomad4 SAS

AF:

0.152

Gnomad4 FIN

AF:

0.0383

Gnomad4 NFE

AF:

0.0778

Gnomad4 OTH

AF:

0.0885

Alfa

AF:

0.0840

Hom.:

1288

Bravo

AF:

0.0634

TwinsUK

AF:

0.0631

AC:

234

ALSPAC

AF:

0.0698

AC:

269

ESP6500AA

AF:

0.0250

AC:

110

ESP6500EA

AF:

0.0879

AC:

756

ExAC

AF:

0.0885

AC:

10748

Asia WGS

AF:

0.163

AC:

568

AN:

3478

EpiCase

AF:

0.0889

EpiControl

AF:

0.0958

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.26

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.43

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.13

T;T;T

Eigen

Benign

0.14

Eigen_PC

Uncertain

0.35

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.79

.;T;.

MetaRNN

Benign

0.0016

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.8

L;L;L

MutationTaster

Benign

0.00065

P;P

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-2.1

N;.;N

REVEL

Benign

0.083

Sift

Uncertain

0.013

D;.;D

Sift4G

Benign

0.22

T;T;T

Polyphen

0.12

B;B;B

Vest4

0.23

MPC

0.14

ClinPred

0.022

GERP RS

6.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.44

gMVP

0.69

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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