dbSNP rs10999147: AIFM2:p.Met135Thr (chr10-70121102-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -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.

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

Publications

25 publications found

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 was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
AIFM2	NM_032797.6 link	c.404T>C	p.Met135Thr	missense_variant	Exon 4 of 9	ENST00000307864.3	NP_116186.1
AIFM2	NM_001198696.2 link	c.404T>C	p.Met135Thr	missense_variant	Exon 4 of 9		NP_001185625.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
AIFM2	ENST00000307864.3 link	c.404T>C	p.Met135Thr	missense_variant	Exon 4 of 9	1	NM_032797.6	ENSP00000312370.1
AIFM2	ENST00000373248.5 link	c.404T>C	p.Met135Thr	missense_variant	Exon 3 of 9	1		ENSP00000362345.1
AIFM2	ENST00000613322.4 link	c.404T>C	p.Met135Thr	missense_variant	Exon 4 of 9	5		ENSP00000478931.1

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

GnomAD2 exomes

AF:

0.0861

AC:

21546

AN:

250222

AF XY:

0.0927

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 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

African (AFR)

AF:

0.0222

AC:

741

AN:

33446

American (AMR)

AF:

0.0464

AC:

2070

AN:

44640

Ashkenazi Jewish (ASJ)

AF:

0.161

AC:

4198

AN:

26122

East Asian (EAS)

AF:

0.142

AC:

5651

AN:

39690

South Asian (SAS)

AF:

0.154

AC:

13255

AN:

86178

European-Finnish (FIN)

AF:

0.0432

AC:

2282

AN:

52770

Middle Eastern (MID)

AF:

0.198

AC:

1139

AN:

5760

European-Non Finnish (NFE)

AF:

0.0779

AC:

86625

AN:

1111870

Other (OTH)

AF:

0.0949

AC:

5727

AN:

60362

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

6432

12865

19297

25730

32162

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3274

6548

9822

13096

16370

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0645

AC:

9802

AN:

151902

Hom.:

459

Cov.:

AF XY:

0.0648

AC XY:

4813

AN XY:

74244

show subpopulations

African (AFR)

AF:

0.0214

AC:

887

AN:

41438

American (AMR)

AF:

0.0626

AC:

955

AN:

15254

Ashkenazi Jewish (ASJ)

AF:

0.169

AC:

585

AN:

3466

East Asian (EAS)

AF:

0.135

AC:

696

AN:

5148

South Asian (SAS)

AF:

0.152

AC:

728

AN:

4804

European-Finnish (FIN)

AF:

0.0383

AC:

404

AN:

10548

Middle Eastern (MID)

AF:

0.153

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0778

AC:

5288

AN:

67926

Other (OTH)

AF:

0.0885

AC:

187

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

440

880

1320

1760

2200

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

128

256

384

512

640

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0805

Hom.:

1822

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

(source)

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

0.0

.;T;.

MetaRNN

Benign

0.0016

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.8

L;L;L

PhyloP100

7.9

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

Vest4

0.23

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

Mutation Taster

=96/4

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over