22-20968548-T-C

Variant names:

• chr22-20968548-T-C
• rs178255
• NM_001386814.1:c.31+573T>C

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+573T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.927 in 152,094 control chromosomes in the GnomAD database, including 65,478 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 0.93 (65478 hom., cov: 30)
• Consequence: AIFM3 NM_001386814.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.323
• Publications: 13 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 = 0.976 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AIFM3	NM_001386814.1	MANE Select	c.31+573T>C		intron	N/A	NP_001373743.1
	AIFM3	NM_144704.3		c.31+573T>C		intron	N/A	NP_653305.1
	AIFM3	NM_001146288.2		c.31+573T>C		intron	N/A	NP_001139760.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AIFM3	ENST00000440238.4	TSL:1 MANE Select	c.31+573T>C		intron	N/A	ENSP00000390798.2
	AIFM3	ENST00000399163.6	TSL:1	c.31+573T>C		intron	N/A	ENSP00000382116.2
	AIFM3	ENST00000399167.6	TSL:2	c.31+573T>C		intron	N/A	ENSP00000382120.2

Frequencies

GnomAD3 genomes AF: 0.927 AC: 140893 AN: 151976 Hom.: 65430 Cov.: 30

Gnomad AFR AF: 0.891

Gnomad AMI AF: 0.961

Gnomad AMR AF: 0.930

Gnomad ASJ AF: 0.882

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.915

Gnomad FIN AF: 0.987

Gnomad MID AF: 0.886

Gnomad NFE AF: 0.937

Gnomad OTH AF: 0.917

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

GnomAD4 genome AF: 0.927 AC: 140996 AN: 152094 Hom.: 65478 Cov.: 30 AF XY: 0.930 AC XY: 69122 AN XY: 74350

African (AFR) AF: 0.891 AC: 36916 AN: 41448

American (AMR) AF: 0.930 AC: 14210 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.882 AC: 3062 AN: 3472

East Asian (EAS) AF: 0.999 AC: 5149 AN: 5156

South Asian (SAS) AF: 0.916 AC: 4414 AN: 4820

European-Finnish (FIN) AF: 0.987 AC: 10474 AN: 10614

Middle Eastern (MID) AF: 0.891 AC: 262 AN: 294

European-Non Finnish (NFE) AF: 0.937 AC: 63699 AN: 67984

Other (OTH) AF: 0.917 AC: 1934 AN: 2110

Alfa AF: 0.931 Hom.: 111822

Bravo AF: 0.922

Asia WGS AF: 0.941 AC: 3275 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.4
DANN	Benign	0.46
PhyloP100		-0.32
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: rs178255; hg19: chr22-21322836;