chr22-20981270-C-T

Variant names:

• chr22-20981270-C-T
• rs7292968
• NM_001386814.1:c.*239C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 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]

ENSG00000285314 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
AIFM3	NM_001386814.1	c.*239C>T		3_prime_UTR_variant	Exon 21 of 21	ENST00000440238.4	NP_001373743.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AIFM3	ENST00000440238.4	c.*239C>T		3_prime_UTR_variant	Exon 21 of 21	1	NM_001386814.1	ENSP00000390798.2

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

African (AFR) AF: 0.352 AC: 4186 AN: 11882

American (AMR) AF: 0.0564 AC: 996 AN: 17644

Ashkenazi Jewish (ASJ) AF: 0.0557 AC: 710 AN: 12754

East Asian (EAS) AF: 0.000384 AC: 11 AN: 28616

South Asian (SAS) AF: 0.0817 AC: 3700 AN: 45270

European-Finnish (FIN) AF: 0.0320 AC: 866 AN: 27024

Middle Eastern (MID) AF: 0.0734 AC: 134 AN: 1826

European-Non Finnish (NFE) AF: 0.0519 AC: 13079 AN: 251778

Other (OTH) AF: 0.0695 AC: 1696 AN: 24420

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

African (AFR) AF: 0.347 AC: 14398 AN: 41518

American (AMR) AF: 0.0785 AC: 1201 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0501 AC: 174 AN: 3470

East Asian (EAS) AF: 0.000965 AC: 5 AN: 5184

South Asian (SAS) AF: 0.0742 AC: 358 AN: 4826

European-Finnish (FIN) AF: 0.0287 AC: 305 AN: 10618

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.0516 AC: 3514 AN: 68036

Other (OTH) AF: 0.111 AC: 234 AN: 2116

Alfa AF: 0.0817 Hom.: 3056

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
PhyloP100		-0.24
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: rs7292968; hg19: chr22-21335559;