chr11-43330041-G-A
Position:
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2
The NM_001142930.2(API5):c.1204G>A(p.Ala402Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000411 in 1,461,412 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: not found (cov: 33)
Exomes 𝑓: 0.0000041 ( 0 hom. )
Consequence
API5
NM_001142930.2 missense
NM_001142930.2 missense
Scores
2
5
10
Clinical Significance
Conservation
PhyloP100: 7.57
Genes affected
API5 (HGNC:594): (apoptosis inhibitor 5) This gene encodes an apoptosis inhibitory protein whose expression prevents apoptosis after growth factor deprivation. This protein suppresses the transcription factor E2F1-induced apoptosis and also interacts with, and negatively regulates Acinus, a nuclear factor involved in apoptotic DNA fragmentation. Its depletion enhances the cytotoxic action of the chemotherapeutic drugs. Multiple alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Aug 2011]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -5 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.41330746).
BS2
High AC in GnomAdExome4 at 6 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
API5 | NM_001142930.2 | c.1204G>A | p.Ala402Thr | missense_variant | 10/14 | ENST00000531273.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
API5 | ENST00000531273.6 | c.1204G>A | p.Ala402Thr | missense_variant | 10/14 | 2 | NM_001142930.2 | P1 | |
ENST00000526220.1 | n.197-703C>T | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 genomes
Cov.:
33
GnomAD3 exomes AF: 0.00000799 AC: 2AN: 250406Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135408
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GnomAD4 exome AF: 0.00000411 AC: 6AN: 1461412Hom.: 0 Cov.: 30 AF XY: 0.00000825 AC XY: 6AN XY: 727000
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GnomAD4 genome Cov.: 33
GnomAD4 genome
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33
ExAC
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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 | Jan 27, 2022 | The c.1204G>A (p.A402T) alteration is located in exon 10 (coding exon 10) of the API5 gene. This alteration results from a G to A substitution at nucleotide position 1204, causing the alanine (A) at amino acid position 402 to be replaced by a threonine (T). 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
Uncertain
DANN
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D;D;D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D;D;D;D
PrimateAI
Pathogenic
T
PROVEAN
Benign
N;N;N;N;N;N
REVEL
Benign
Sift
Uncertain
D;D;D;D;D;D
Sift4G
Benign
T;T;T;T;T;T
Polyphen
0.96, 0.95
.;D;.;P;P;.
Vest4
MutPred
0.33
.;Gain of relative solvent accessibility (P = 0.0289);.;Gain of relative solvent accessibility (P = 0.0289);Gain of relative solvent accessibility (P = 0.0289);.;
MVP
MPC
0.78
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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Calibrated prediction
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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