chr22-20969894-T-G

Variant names:

• chr22-20969894-T-G
• rs178259
• NM_001386814.1:c.31+1919T>G

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+1919T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.953 in 151,978 control chromosomes in the GnomAD database, including 69,122 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 0.95 (69122 hom., cov: 27)
• Consequence: AIFM3 NM_001386814.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.41
• 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=-0.95).
• 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 rank	MANE	Protein	UniProt
AIFM3	NM_001386814.1	c.31+1919T>G		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+1919T>G		intron_variant	Intron 2 of 20	1	NM_001386814.1	ENSP00000390798.2

Frequencies

GnomAD3 genomes AF: 0.953 AC: 144758 AN: 151860 Hom.: 69078 Cov.: 27

Gnomad AFR AF: 0.912

Gnomad AMI AF: 0.999

Gnomad AMR AF: 0.965

Gnomad ASJ AF: 0.935

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.919

Gnomad FIN AF: 0.997

Gnomad MID AF: 0.939

Gnomad NFE AF: 0.968

Gnomad OTH AF: 0.956

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

GnomAD4 genome AF: 0.953 AC: 144861 AN: 151978 Hom.: 69122 Cov.: 27 AF XY: 0.954 AC XY: 70896 AN XY: 74292

African (AFR) AF: 0.912 AC: 37755 AN: 41406

American (AMR) AF: 0.965 AC: 14729 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.935 AC: 3243 AN: 3470

East Asian (EAS) AF: 0.999 AC: 5130 AN: 5136

South Asian (SAS) AF: 0.919 AC: 4418 AN: 4806

European-Finnish (FIN) AF: 0.997 AC: 10570 AN: 10602

Middle Eastern (MID) AF: 0.945 AC: 276 AN: 292

European-Non Finnish (NFE) AF: 0.968 AC: 65813 AN: 67974

Other (OTH) AF: 0.955 AC: 2016 AN: 2112

Alfa AF: 0.960 Hom.: 28331

Bravo AF: 0.951

Asia WGS AF: 0.944 AC: 3284 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.42
DANN	Benign	0.72
PhyloP100		-1.4
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: rs178259; hg19: chr22-21324182;