chr12-98665674-T-C
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_181861.2(APAF1):c.1077T>C(p.Tyr359=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00454 in 1,613,998 control chromosomes in the GnomAD database, including 266 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.024 ( 136 hom., cov: 31)
Exomes 𝑓: 0.0025 ( 130 hom. )
Consequence
APAF1
NM_181861.2 synonymous
NM_181861.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.00400
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.55).
BP6
?
Variant 12-98665674-T-C is Benign according to our data. Variant chr12-98665674-T-C is described in ClinVar as [Benign]. Clinvar id is 773029.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0823 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
APAF1 | NM_181861.2 | c.1077T>C | p.Tyr359= | synonymous_variant | 8/27 | ENST00000551964.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
APAF1 | ENST00000551964.6 | c.1077T>C | p.Tyr359= | synonymous_variant | 8/27 | 1 | NM_181861.2 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0241 AC: 3668AN: 152100Hom.: 136 Cov.: 31
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GnomAD3 exomes AF: 0.00636 AC: 1599AN: 251274Hom.: 51 AF XY: 0.00466 AC XY: 633AN XY: 135804
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GnomAD4 exome AF: 0.00250 AC: 3652AN: 1461780Hom.: 130 Cov.: 32 AF XY: 0.00217 AC XY: 1581AN XY: 727194
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GnomAD4 genome ? AF: 0.0242 AC: 3677AN: 152218Hom.: 136 Cov.: 31 AF XY: 0.0230 AC XY: 1713AN XY: 74450
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Dec 31, 2019 | - - |
APAF1-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Feb 21, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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BayesDel_noAF
Benign
Cadd
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Dann
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Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at