Genetic Variant AIFM3:p.Arg24Gln (chr22-20973346-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001386814.1(AIFM3):c.71G>A(p.Arg24Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000523 in 1,454,216 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)

Exomes 𝑓: 0.000052 ( 0 hom. )

Consequence

AIFM3
NM_001386814.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.49

Publications

1 publications found

Variant links:

Genes affected

AIFM3 (HGNC:26398): (apoptosis inducing factor mitochondria associated 3) Predicted to enable several functions, including 2 iron, 2 sulfur cluster binding activity; flavin adenine dinucleotide binding activity; and metal ion binding activity. Involved in execution phase of apoptosis. Located in cytosol; endoplasmic reticulum; and mitochondrial inner membrane. [provided by Alliance of Genome Resources, Apr 2022]

AIFM3 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.15380874).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001386814.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
AIFM3	NM_001386814.1	MANE Select	c.71G>A	p.Arg24Gln	missense	Exon 3 of 21	NP_001373743.1	Q96NN9-1
AIFM3	NM_144704.3		c.71G>A	p.Arg24Gln	missense	Exon 3 of 21	NP_653305.1	Q96NN9-1
AIFM3	NM_001146288.2		c.89G>A	p.Arg30Gln	missense	Exon 3 of 20	NP_001139760.1	Q96NN9-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
AIFM3	ENST00000440238.4	TSL:1 MANE Select	c.71G>A	p.Arg24Gln	missense	Exon 3 of 21	ENSP00000390798.2	Q96NN9-1
AIFM3	ENST00000399163.6	TSL:1	c.71G>A	p.Arg24Gln	missense	Exon 3 of 20	ENSP00000382116.2	Q96NN9-3
AIFM3	ENST00000399167.6	TSL:2	c.71G>A	p.Arg24Gln	missense	Exon 3 of 21	ENSP00000382120.2	Q96NN9-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000850

AC:

AN:

235166

AF XY:

0.0000156

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000190

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000523

AC:

AN:

1454216

Hom.:

Cov.:

AF XY:

0.0000498

AC XY:

AN XY:

722946

show subpopulations

African (AFR)

AF:

0.0000300

AC:

AN:

33284

American (AMR)

AF:

0.00

AC:

AN:

43632

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25878

East Asian (EAS)

AF:

0.00

AC:

AN:

39332

South Asian (SAS)

AF:

0.00

AC:

AN:

85074

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52232

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5728

European-Non Finnish (NFE)

AF:

0.0000658

AC:

AN:

1108950

Other (OTH)

AF:

0.0000333

AC:

AN:

60106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000826

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.084

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.43

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.020

Eigen

Benign

0.073

Eigen_PC

Benign

0.13

FATHMM_MKL

Benign

0.74

LIST_S2

Uncertain

0.93

M_CAP

Benign

0.042

MetaRNN

Benign

0.15

MetaSVM

Benign

-0.96

MutationAssessor

Benign

1.1

PhyloP100

4.5

PROVEAN

Benign

-0.44

REVEL

Benign

0.16

Sift

Uncertain

0.0080

Sift4G

Benign

0.20

Polyphen

0.93

Vest4

0.31

MutPred

0.14

Gain of sheet (P = 0.039)

MVP

0.62

MPC

0.66

ClinPred

0.34

GERP RS

4.2

Varity_R

0.14

gMVP

0.28

Mutation Taster

=85/15

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over