chr10-70114228-C-G

Variant names:

• chr10-70114228-C-G
• NM_032797.6:c.1072G>C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_032797.6(AIFM2):​c.1072G>C​(p.Asp358His) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,734 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: AIFM2 NM_032797.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.25

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.817

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AIFM2	NM_032797.6	c.1072G>C	p.Asp358His	missense_variant	Exon 9 of 9	ENST00000307864.3	NP_116186.1
AIFM2	NM_001198696.2	c.1072G>C	p.Asp358His	missense_variant	Exon 9 of 9		NP_001185625.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AIFM2	ENST00000307864.3	c.1072G>C	p.Asp358His	missense_variant	Exon 9 of 9	1	NM_032797.6	ENSP00000312370.1
AIFM2	ENST00000373248.5	c.1072G>C	p.Asp358His	missense_variant	Exon 8 of 9	1		ENSP00000362345.1
AIFM2	ENST00000613322.4	c.1072G>C	p.Asp358His	missense_variant	Exon 9 of 9	5		ENSP00000478931.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461734 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 727196

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.71
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.090
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.55	D;D;D
Eigen	Pathogenic	0.70
Eigen_PC	Pathogenic	0.69
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.88	.;D;.
M_CAP	Benign	0.025	D
MetaRNN	Pathogenic	0.82	D;D;D
MetaSVM	Benign	-0.81	T
MutationAssessor	Pathogenic	3.0	M;M;M
PrimateAI	Uncertain	0.57	T
PROVEAN	Pathogenic	-4.6	D;.;D
REVEL	Uncertain	0.39
Sift	Uncertain	0.0080	D;.;D
Sift4G	Uncertain	0.012	D;D;D
Polyphen		1.0	D;D;D
Vest4		0.76
MutPred		0.76		Loss of sheet (P = 0.0043);Loss of sheet (P = 0.0043);Loss of sheet (P = 0.0043);
MVP		0.70
MPC		0.54
ClinPred		0.99	D
GERP RS		5.6
Varity_R		0.35
gMVP		0.89

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-71873984;