rs373088207

Variant names:

• chr22-20973364-C-A
• rs373088207
• NM_001386814.1:c.89C>A

Your query was ambiguous. Multiple possible variants found:

• chr22-20973364-C-A
• chr22-20973364-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001386814.1(AIFM3):​c.89C>A​(p.Ser30*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,456,992 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: AIFM3 NM_001386814.1 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.21
• Publications: 0 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001386814.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AIFM3	NM_001386814.1	MANE Select	c.89C>A	p.Ser30*	stop_gained	Exon 3 of 21	NP_001373743.1	Q96NN9-1
	AIFM3	NM_144704.3		c.89C>A	p.Ser30*	stop_gained	Exon 3 of 21	NP_653305.1	Q96NN9-1
	AIFM3	NM_001146288.2		c.107C>A	p.Ser36*	stop_gained	Exon 3 of 20	NP_001139760.1	Q96NN9-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AIFM3	ENST00000440238.4	TSL:1 MANE Select	c.89C>A	p.Ser30*	stop_gained	Exon 3 of 21	ENSP00000390798.2	Q96NN9-1
	AIFM3	ENST00000399163.6	TSL:1	c.89C>A	p.Ser30*	stop_gained	Exon 3 of 20	ENSP00000382116.2	Q96NN9-3
	AIFM3	ENST00000399167.6	TSL:2	c.89C>A	p.Ser30*	stop_gained	Exon 3 of 21	ENSP00000382120.2	Q96NN9-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1456992 Hom.: 0 Cov.: 35 AF XY: 0.00000138 AC XY: 1 AN XY: 724478

African (AFR) AF: 0.00 AC: 0 AN: 33394

American (AMR) AF: 0.00 AC: 0 AN: 44212

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25982

East Asian (EAS) AF: 0.00 AC: 0 AN: 39516

South Asian (SAS) AF: 0.00 AC: 0 AN: 85426

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52342

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5674

European-Non Finnish (NFE) AF: 9.01e-7 AC: 1 AN: 1110246

Other (OTH) AF: 0.00 AC: 0 AN: 60200

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.44	D
BayesDel_noAF	Pathogenic	0.40
CADD	Pathogenic	37
DANN	Uncertain	0.98
Eigen	Benign	0.15
Eigen_PC	Benign	-0.11
FATHMM_MKL	Pathogenic	0.98	D
PhyloP100		2.2
Vest4		0.34
GERP RS		2.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=37/163	disease causing (fs/PTC)

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: rs373088207; hg19: chr22-21327653;