22-20975977-T-C

Variant names:

• chr22-20975977-T-C
• rs178268
• NM_001386814.1:c.807+199T>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.807+199T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.608 in 152,146 control chromosomes in the GnomAD database, including 29,599 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 0.61 (29599 hom., cov: 33)
• Consequence: AIFM3 NM_001386814.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.398
• Publications: 3 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 = 0.797 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.807+199T>C		intron	N/A	NP_001373743.1
	AIFM3	NM_144704.3		c.807+199T>C		intron	N/A	NP_653305.1
	AIFM3	NM_001146288.2		c.825+199T>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.807+199T>C		intron	N/A	ENSP00000390798.2
	AIFM3	ENST00000399163.6	TSL:1	c.807+199T>C		intron	N/A	ENSP00000382116.2
	AIFM3	ENST00000399167.6	TSL:2	c.807+199T>C		intron	N/A	ENSP00000382120.2

Frequencies

GnomAD3 genomes AF: 0.608 AC: 92366 AN: 152028 Hom.: 29558 Cov.: 33

Gnomad AFR AF: 0.799

Gnomad AMI AF: 0.436

Gnomad AMR AF: 0.545

Gnomad ASJ AF: 0.533

Gnomad EAS AF: 0.817

Gnomad SAS AF: 0.696

Gnomad FIN AF: 0.440

Gnomad MID AF: 0.595

Gnomad NFE AF: 0.515

Gnomad OTH AF: 0.609

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

GnomAD4 genome AF: 0.608 AC: 92462 AN: 152146 Hom.: 29599 Cov.: 33 AF XY: 0.605 AC XY: 44998 AN XY: 74386

African (AFR) AF: 0.799 AC: 33206 AN: 41538

American (AMR) AF: 0.545 AC: 8330 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.533 AC: 1846 AN: 3466

East Asian (EAS) AF: 0.818 AC: 4222 AN: 5162

South Asian (SAS) AF: 0.696 AC: 3356 AN: 4824

European-Finnish (FIN) AF: 0.440 AC: 4652 AN: 10580

Middle Eastern (MID) AF: 0.578 AC: 170 AN: 294

European-Non Finnish (NFE) AF: 0.515 AC: 35000 AN: 67974

Other (OTH) AF: 0.610 AC: 1285 AN: 2108

Alfa AF: 0.556 Hom.: 17968

Bravo AF: 0.626

Asia WGS AF: 0.749 AC: 2602 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	2.8
DANN	Benign	0.28
PhyloP100		-0.40
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs178268; hg19: chr22-21330266;