22-20974782-G-A
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Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001386814.1(AIFM3):c.686G>A(p.Arg229Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000298 in 1,613,234 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000031 ( 0 hom. )
Consequence
AIFM3
NM_001386814.1 missense
NM_001386814.1 missense
Scores
6
11
Clinical Significance
Conservation
PhyloP100: 3.81
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]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.26006493).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AIFM3 | NM_001386814.1 | c.686G>A | p.Arg229Gln | missense_variant | 8/21 | ENST00000440238.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AIFM3 | ENST00000440238.4 | c.686G>A | p.Arg229Gln | missense_variant | 8/21 | 1 | NM_001386814.1 | A1 |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152168Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000478 AC: 12AN: 250862Hom.: 0 AF XY: 0.0000295 AC XY: 4AN XY: 135708
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GnomAD4 exome AF: 0.0000308 AC: 45AN: 1460948Hom.: 0 Cov.: 35 AF XY: 0.0000220 AC XY: 16AN XY: 726788
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GnomAD4 genome AF: 0.0000197 AC: 3AN: 152286Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74468
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 20, 2021 | The c.686G>A (p.R229Q) alteration is located in exon 8 (coding exon 7) of the AIFM3 gene. This alteration results from a G to A substitution at nucleotide position 686, causing the arginine (R) at amino acid position 229 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;.;.;.;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
M_CAP
Benign
D
MetaRNN
Benign
T;T;T;T;T
MetaSVM
Uncertain
T
MutationAssessor
Benign
L;L;.;.;L
MutationTaster
Benign
D;D;D;D;D;D
PROVEAN
Benign
N;N;N;N;N
REVEL
Benign
Sift
Benign
T;T;T;T;T
Sift4G
Benign
T;T;T;T;T
Polyphen
P;P;.;P;P
Vest4
MutPred
Loss of phosphorylation at T226 (P = 0.0773);Loss of phosphorylation at T226 (P = 0.0773);Loss of phosphorylation at T226 (P = 0.0773);.;Loss of phosphorylation at T226 (P = 0.0773);
MVP
MPC
ClinPred
T
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gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at