22-20969894-T-G

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
AIFM3	NM_001386814.1	c.31+1919T>G		intron_variant		ENST00000440238.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AIFM3	ENST00000440238.4	c.31+1919T>G		intron_variant		1	NM_001386814.1	A1

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

Gnomad4 AFR AF: 0.912

Gnomad4 AMR AF: 0.965

Gnomad4 ASJ AF: 0.935

Gnomad4 EAS AF: 0.999

Gnomad4 SAS AF: 0.919

Gnomad4 FIN AF: 0.997

Gnomad4 NFE AF: 0.968

Gnomad4 OTH AF: 0.955

Alfa AF: 0.959 Hom.: 16709

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

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: rs178259; hg19: chr22-21324182;