rs7292968

chr22-20981270-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001386814.1(AIFM3):c.*239C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0795 in 573,494 control chromosomes in the GnomAD database, including 4,140 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 0.13 (2737 hom., cov: 34)
  • Exomes 𝑓: 0.060 (1403 hom.)
• Consequence: AIFM3 NM_001386814.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.236

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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.342 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AIFM3	NM_001386814.1	c.*239C>T		3_prime_UTR_variant	21/21	ENST00000440238.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AIFM3	ENST00000440238.4	c.*239C>T		3_prime_UTR_variant	21/21	1	NM_001386814.1	A1

Frequencies

GnomAD3 genomes AF: 0.133 AC: 20189 AN: 152162 Hom.: 2731 Cov.: 34

Gnomad AFR AF: 0.347

Gnomad AMI AF: 0.0351

Gnomad AMR AF: 0.0787

Gnomad ASJ AF: 0.0501

Gnomad EAS AF: 0.000962

Gnomad SAS AF: 0.0729

Gnomad FIN AF: 0.0287

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0516

Gnomad OTH AF: 0.110

GnomAD4 exome AF: 0.0602 AC: 25378 AN: 421214 Hom.: 1403 Cov.: 4 AF XY: 0.0614 AC XY: 13594 AN XY: 221460

Gnomad4 AFR exome AF: 0.352

Gnomad4 AMR exome AF: 0.0564

Gnomad4 ASJ exome AF: 0.0557

Gnomad4 EAS exome AF: 0.000384

Gnomad4 SAS exome AF: 0.0817

Gnomad4 FIN exome AF: 0.0320

Gnomad4 NFE exome AF: 0.0519

Gnomad4 OTH exome AF: 0.0695

GnomAD4 genome AF: 0.133 AC: 20233 AN: 152280 Hom.: 2737 Cov.: 34 AF XY: 0.128 AC XY: 9563 AN XY: 74466

Gnomad4 AFR AF: 0.347

Gnomad4 AMR AF: 0.0785

Gnomad4 ASJ AF: 0.0501

Gnomad4 EAS AF: 0.000965

Gnomad4 SAS AF: 0.0742

Gnomad4 FIN AF: 0.0287

Gnomad4 NFE AF: 0.0516

Gnomad4 OTH AF: 0.111

Alfa AF: 0.0612 Hom.: 938

Bravo AF: 0.144

Asia WGS AF: 0.0560 AC: 194 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	12
Dann	Benign	0.53

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: rs7292968; hg19: chr22-21335559;