22-20968548-T-C

Position:

• chr22-20968548-T-C

Variant summary

Our verdict is Benign. Variant got -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

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]

AIFM3 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AIFM3	NM_001386814.1	c.31+573T>C		intron_variant		ENST00000440238.4	NP_001373743.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AIFM3	ENST00000440238.4	c.31+573T>C		intron_variant		1	NM_001386814.1	ENSP00000390798.2

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

Gnomad4 AFR AF: 0.891

Gnomad4 AMR AF: 0.930

Gnomad4 ASJ AF: 0.882

Gnomad4 EAS AF: 0.999

Gnomad4 SAS AF: 0.916

Gnomad4 FIN AF: 0.987

Gnomad4 NFE AF: 0.937

Gnomad4 OTH AF: 0.917

Alfa AF: 0.931 Hom.: 84297

Bravo AF: 0.922

Asia WGS AF: 0.941 AC: 3275 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	3.4
DANN	Benign	0.46

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: rs178255; hg19: chr22-21322836;