chr12-98665576-A-G
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_181861.2(APAF1):āc.979A>Gā(p.Ile327Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,461,518 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 (ā ).
Frequency
Genomes: not found (cov: 31)
Exomes š: 0.0000027 ( 0 hom. )
Consequence
APAF1
NM_181861.2 missense
NM_181861.2 missense
Scores
1
2
16
Clinical Significance
Conservation
PhyloP100: 5.02
Genes affected
APAF1 (HGNC:576): (apoptotic peptidase activating factor 1) This gene encodes a cytoplasmic protein that initiates apoptosis. This protein contains several copies of the WD-40 domain, a caspase recruitment domain (CARD), and an ATPase domain (NB-ARC). Upon binding cytochrome c and dATP, this protein forms an oligomeric apoptosome. The apoptosome binds and cleaves caspase 9 preproprotein, releasing its mature, activated form. Activated caspase 9 stimulates the subsequent caspase cascade that commits the cell to apoptosis. Alternative splicing results in several transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
APAF1 | NM_181861.2 | c.979A>G | p.Ile327Val | missense_variant | 8/27 | ENST00000551964.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
APAF1 | ENST00000551964.6 | c.979A>G | p.Ile327Val | missense_variant | 8/27 | 1 | NM_181861.2 | P1 |
Frequencies
GnomAD3 genomes Cov.: 31
GnomAD3 genomes
Cov.:
31
GnomAD3 exomes AF: 0.0000120 AC: 3AN: 250988Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135766
GnomAD3 exomes
AF:
AC:
3
AN:
250988
Hom.:
AF XY:
AC XY:
1
AN XY:
135766
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00000274 AC: 4AN: 1461518Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1AN XY: 727076
GnomAD4 exome
AF:
AC:
4
AN:
1461518
Hom.:
Cov.:
32
AF XY:
AC XY:
1
AN XY:
727076
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome Cov.: 31
GnomAD4 genome
Cov.:
31
ExAC
AF:
AC:
1
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 | Sep 20, 2023 | The c.979A>G (p.I327V) alteration is located in exon 8 (coding exon 7) of the APAF1 gene. This alteration results from a A to G substitution at nucleotide position 979, causing the isoleucine (I) at amino acid position 327 to be replaced by a valine (V). 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
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T;.;.;.;.;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
D;T;T;D;.;T
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;L;.;.;L;.
MutationTaster
Benign
D;D;D;D;D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N;N;N;N
REVEL
Benign
Sift
Benign
D;D;D;D;D;D
Sift4G
Benign
T;T;T;T;T;T
Polyphen
B;B;B;P;B;.
Vest4
MutPred
Gain of catalytic residue at I327 (P = 5e-04);Gain of catalytic residue at I327 (P = 5e-04);.;.;Gain of catalytic residue at I327 (P = 5e-04);Gain of catalytic residue at I327 (P = 5e-04);
MVP
MPC
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_AG_spliceai
Position offset: -8
Find out detailed SpliceAI scores and Pangolin per-transcript scores at