10-70114943-C-A

Variant names:

• chr10-70114943-C-A
• rs750119679
• NM_032797.6:c.947G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_032797.6(AIFM2):​c.947G>T​(p.Arg316Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,772 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. R316Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: AIFM2 NM_032797.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.77
• Publications: 2 publications found

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]

ACMG classification

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=0.17888814).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032797.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AIFM2	NM_032797.6	MANE Select	c.947G>T	p.Arg316Leu	missense	Exon 8 of 9	NP_116186.1	Q9BRQ8-1
	AIFM2	NM_001198696.2		c.947G>T	p.Arg316Leu	missense	Exon 8 of 9	NP_001185625.1	Q9BRQ8-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AIFM2	ENST00000307864.3	TSL:1 MANE Select	c.947G>T	p.Arg316Leu	missense	Exon 8 of 9	ENSP00000312370.1	Q9BRQ8-1
	AIFM2	ENST00000373248.5	TSL:1	c.947G>T	p.Arg316Leu	missense	Exon 7 of 9	ENSP00000362345.1	Q9BRQ8-1
	AIFM2	ENST00000856761.1		c.1181G>T	p.Arg394Leu	missense	Exon 8 of 9	ENSP00000526820.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251012 AF XY: 0.00

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461772 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727180

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86232

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53386

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111974

Other (OTH) AF: 0.00 AC: 0 AN: 60384

GnomAD4 genome Cov.: 33

ExAC AF: 0.0000165 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.42	T
Eigen	Benign	-0.31
Eigen_PC	Benign	-0.18
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.85	D
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	2.0	M
PhyloP100		2.8
PrimateAI	Benign	0.40	T
PROVEAN	Uncertain	-3.4	D
REVEL	Benign	0.16
Sift	Benign	0.055	T
Sift4G	Uncertain	0.032	D
Polyphen		0.19	B
Vest4		0.12
MutPred		0.54		Loss of methylation at K314 (P = 0.035)
MVP		0.55
MPC		0.15
ClinPred		0.85	D
GERP RS		3.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.11
gMVP		0.72
Mutation Taster		=85/15	polymorphism

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

Other links and lift over

dbSNP: rs750119679; hg19: chr10-71874699;