22-20973827-G-A

Variant names:

• chr22-20973827-G-A
• rs1161672524
• NM_001386814.1:c.315G>A
• AIFM3 p.Leu105Leu

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_001386814.1(AIFM3):​c.315G>A​(p.Leu105Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: AIFM3 NM_001386814.1 synonymous
• 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: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BP7: Synonymous conserved (PhyloP=2.21 with no splicing effect.

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.315G>A	p.Leu105Leu	synonymous	Exon 4 of 21	NP_001373743.1	Q96NN9-1
	AIFM3	NM_144704.3		c.315G>A	p.Leu105Leu	synonymous	Exon 4 of 21	NP_653305.1	Q96NN9-1
	AIFM3	NM_001146288.2		c.333G>A	p.Leu111Leu	synonymous	Exon 4 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.315G>A	p.Leu105Leu	synonymous	Exon 4 of 21	ENSP00000390798.2	Q96NN9-1
	AIFM3	ENST00000399163.6	TSL:1	c.315G>A	p.Leu105Leu	synonymous	Exon 4 of 20	ENSP00000382116.2	Q96NN9-3
	AIFM3	ENST00000399167.6	TSL:2	c.315G>A	p.Leu105Leu	synonymous	Exon 4 of 21	ENSP00000382120.2	Q96NN9-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00 AC: 0 AN: 195472 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1426172 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 705778

African (AFR) AF: 0.00 AC: 0 AN: 32878

American (AMR) AF: 0.00 AC: 0 AN: 39816

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25048

East Asian (EAS) AF: 0.00 AC: 0 AN: 38224

South Asian (SAS) AF: 0.00 AC: 0 AN: 80672

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51162

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5436

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1093958

Other (OTH) AF: 0.00 AC: 0 AN: 58978

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	12
DANN	Benign	0.82
PhyloP100		2.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs1161672524;

hg19: chr22-21328116;