10-70114943-C-G

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_032797.6(AIFM2):​c.947G>C​(p.Arg316Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,192 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
• Consequence: AIFM2 NM_032797.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.77

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

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.31579107).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AIFM2	NM_032797.6	c.947G>C	p.Arg316Pro	missense_variant	Exon 8 of 9	ENST00000307864.3	NP_116186.1
AIFM2	NM_001198696.2	c.947G>C	p.Arg316Pro	missense_variant	Exon 8 of 9		NP_001185625.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AIFM2	ENST00000307864.3	c.947G>C	p.Arg316Pro	missense_variant	Exon 8 of 9	1	NM_032797.6	ENSP00000312370.1
AIFM2	ENST00000373248.5	c.947G>C	p.Arg316Pro	missense_variant	Exon 7 of 9	1		ENSP00000362345.1
AIFM2	ENST00000613322.4	c.947G>C	p.Arg316Pro	missense_variant	Exon 8 of 9	5		ENSP00000478931.1
AIFM2	ENST00000482166.1	n.784G>C		non_coding_transcript_exon_variant	Exon 4 of 4	3

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152192 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152192 Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1 AN XY: 74344

Gnomad4 AFR AF: 0.0000241

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.75
BayesDel_addAF	Benign	-0.079	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.22	T;T;T
Eigen	Benign	-0.16
Eigen_PC	Benign	-0.077
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.82	.;T;.
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.32	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L;L;L
PrimateAI	Benign	0.42	T
PROVEAN	Uncertain	-2.5	N;.;N
REVEL	Benign	0.18
Sift	Benign	0.046	D;.;D
Sift4G	Uncertain	0.032	D;D;D
Polyphen		0.54	P;P;P
Vest4		0.39
MutPred		0.52		Gain of glycosylation at R316 (P = 0.0316);Gain of glycosylation at R316 (P = 0.0316);Gain of glycosylation at R316 (P = 0.0316);
MVP		0.65
MPC		0.21
ClinPred		0.91	D
GERP RS		3.7
Varity_R		0.42
gMVP		0.88

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

Other links and lift over

dbSNP: rs750119679; hg19: chr10-71874699;