rs178260

Variant names:

• chr22-20970019-G-T
• rs178260
• NM_001386814.1:c.31+2044G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001386814.1(AIFM3):​c.31+2044G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.151 in 152,112 control chromosomes in the GnomAD database, including 2,004 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.15 (2004 hom., cov: 33)
• Consequence: AIFM3 NM_001386814.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.93
• Publications: 8 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.403 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AIFM3	NM_001386814.1	c.31+2044G>T		intron_variant	Intron 2 of 20	ENST00000440238.4	NP_001373743.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AIFM3	ENST00000440238.4	c.31+2044G>T		intron_variant	Intron 2 of 20	1	NM_001386814.1	ENSP00000390798.2

Frequencies

GnomAD3 genomes AF: 0.151 AC: 22988 AN: 151994 Hom.: 2004 Cov.: 33

Gnomad AFR AF: 0.144

Gnomad AMI AF: 0.0998

Gnomad AMR AF: 0.192

Gnomad ASJ AF: 0.0767

Gnomad EAS AF: 0.417

Gnomad SAS AF: 0.222

Gnomad FIN AF: 0.174

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.123

Gnomad OTH AF: 0.148

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.151 AC: 23006 AN: 152112 Hom.: 2004 Cov.: 33 AF XY: 0.157 AC XY: 11682 AN XY: 74350

African (AFR) AF: 0.144 AC: 5986 AN: 41504

American (AMR) AF: 0.192 AC: 2935 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0767 AC: 266 AN: 3470

East Asian (EAS) AF: 0.418 AC: 2156 AN: 5162

South Asian (SAS) AF: 0.220 AC: 1063 AN: 4822

European-Finnish (FIN) AF: 0.174 AC: 1842 AN: 10580

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.123 AC: 8330 AN: 67974

Other (OTH) AF: 0.148 AC: 313 AN: 2112

Alfa AF: 0.137 Hom.: 890

Bravo AF: 0.158

Asia WGS AF: 0.293 AC: 1018 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.19
DANN	Benign	0.63
PhyloP100		-1.9
Mutation Taster		=100/0	polymorphism (auto)

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: rs178260; hg19: chr22-21324308;