11-43335881-C-A

Variant names:

• chr11-43335881-C-A
• rs772388129
• NM_001142930.2:c.1379C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001142930.2(API5):​c.1379C>A​(p.Thr460Lys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000055 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: API5 NM_001142930.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.52
• Publications: 0 publications found

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]

ENSG00000254907 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13669491).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001142930.2. 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
	API5	NM_001142930.2	MANE Select	c.1379C>A	p.Thr460Lys	missense	Exon 13 of 14	NP_001136402.1	Q9BZZ5-4
	API5	NM_006595.4		c.1379C>A	p.Thr460Lys	missense	Exon 13 of 14	NP_006586.1	Q9BZZ5-2
	API5	NM_001142931.2		c.1217C>A	p.Thr406Lys	missense	Exon 12 of 13	NP_001136403.1	Q9BZZ5-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	API5	ENST00000531273.6	TSL:2 MANE Select	c.1379C>A	p.Thr460Lys	missense	Exon 13 of 14	ENSP00000431391.1	Q9BZZ5-4
	API5	ENST00000378852.7	TSL:1	c.1379C>A	p.Thr460Lys	missense	Exon 13 of 14	ENSP00000368129.3	Q9BZZ5-2
	API5	ENST00000455725.6	TSL:2	c.1346C>A	p.Thr449Lys	missense	Exon 14 of 15	ENSP00000399341.2	Q9BZZ5-6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000807 AC: 2 AN: 247874 AF XY: 0.0000149

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: AS_VQSR AF: 0.00000548 AC: 8 AN: 1458956 Hom.: 0 Cov.: 31 AF XY: 0.00000827 AC XY: 6 AN XY: 725640

African (AFR) AF: 0.00 AC: 0 AN: 33314

American (AMR) AF: 0.00 AC: 0 AN: 44096

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25962

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39674

South Asian (SAS) AF: 0.0000701 AC: 6 AN: 85534

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53360

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5430

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111348

Other (OTH) AF: 0.00 AC: 0 AN: 60238

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 1

Bravo AF: 0.00000378

ExAC AF: 0.0000165 AC: 2

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.36
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	23
DANN	Benign	0.93
DEOGEN2	Benign	0.035	T
Eigen	Benign	-0.054
Eigen_PC	Benign	0.15
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.34	N
PhyloP100		4.5
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-0.87	N
REVEL	Benign	0.088
Sift	Benign	0.48	T
Sift4G	Benign	0.96	T
Polyphen		0.010	B
Vest4		0.38
MutPred		0.38		Gain of ubiquitination at T460 (P = 0.0029)
MVP		0.34
MPC		0.89
ClinPred		0.27	T
GERP RS		5.2
Varity_R		0.16
gMVP		0.68
Mutation Taster		=39/61	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs772388129; hg19: chr11-43357431;