Variant 10-70114970-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_032797.6(AIFM2):c.920C>T(p.Ala307Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000571 in 1,614,176 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00040 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00059 ( 2 hom. )

Consequence

AIFM2
NM_032797.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.32

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 Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.09162095).

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AIFM2	NM_032797.6 linkuse as main transcript	c.920C>T	p.Ala307Val	missense_variant	8/9	ENST00000307864.3	NP_116186.1
AIFM2	NM_001198696.2 linkuse as main transcript	c.920C>T	p.Ala307Val	missense_variant	8/9		NP_001185625.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AIFM2	ENST00000307864.3 linkuse as main transcript	c.920C>T	p.Ala307Val	missense_variant	8/9	1	NM_032797.6	ENSP00000312370	P1	Q9BRQ8-1
AIFM2	ENST00000373248.5 linkuse as main transcript	c.920C>T	p.Ala307Val	missense_variant	7/9	1		ENSP00000362345	P1	Q9BRQ8-1
AIFM2	ENST00000613322.4 linkuse as main transcript	c.920C>T	p.Ala307Val	missense_variant	8/9	5		ENSP00000478931	P1	Q9BRQ8-1
AIFM2	ENST00000482166.1 linkuse as main transcript	n.757C>T		non_coding_transcript_exon_variant	4/4	3

Frequencies

GnomAD3 genomes

AF:

0.000401

AC:

AN:

152236

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000827

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000764

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000378

AC:

AN:

251224

Hom.:

AF XY:

0.000486

AC XY:

AN XY:

135816

show subpopulations

Gnomad AFR exome

AF:

0.0000616

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000981

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.000519

Gnomad OTH exome

AF:

0.000489

GnomAD4 exome

AF:

0.000588

AC:

860

AN:

1461822

Hom.:

Cov.:

AF XY:

0.000606

AC XY:

441

AN XY:

727210

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

Gnomad4 AMR exome

AF:

0.0000894

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000916

Gnomad4 FIN exome

AF:

0.000131

Gnomad4 NFE exome

AF:

0.000658

Gnomad4 OTH exome

AF:

0.000580

GnomAD4 genome

AF:

0.000400

AC:

AN:

152354

Hom.:

Cov.:

AF XY:

0.000309

AC XY:

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.0000481

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000828

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.000764

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000585

Hom.:

Bravo

AF:

0.000348

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00130

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000814

AC:

ExAC

AF:

0.000371

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.000545

EpiControl

AF:

0.000296

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 19, 2022

The c.920C>T (p.A307V) alteration is located in exon 8 (coding exon 7) of the AIFM2 gene. This alteration results from a C to T substitution at nucleotide position 920, causing the alanine (A) at amino acid position 307 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.18

T;T;T

Eigen

Benign

0.026

Eigen_PC

Benign

0.17

FATHMM_MKL

Uncertain

0.90

LIST_S2

Uncertain

0.88

.;D;.

M_CAP

Benign

0.011

MetaRNN

Benign

0.092

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.0

M;M;M

MutationTaster

Benign

0.52

N;N

PrimateAI

Benign

0.33

PROVEAN

Benign

-1.9

N;.;N

REVEL

Benign

0.060

Sift

Benign

0.28

T;.;T

Sift4G

Benign

0.26

T;T;T

Polyphen

0.072

B;B;B

Vest4

0.20

MVP

0.51

MPC

0.12

ClinPred

0.018

GERP RS

5.0

Varity_R

0.17

gMVP

0.54

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