Genetic Variant API5:p.Glu458Lys (chr11-43335874-G-A) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001142930.2(API5):c.1372G>A(p.Glu458Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000077 in 1,610,130 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 0.000046 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000080 ( 0 hom. )

Consequence

API5
NM_001142930.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.48

Publications

0 publications found

Variant links:

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]

API5 links:

ENSG00000254907 (HGNC:):

ENSG00000254907 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.18413684).

BS2

High AC in GnomAd4 at 7 AD gene.

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
API5	NM_001142930.2	MANE Select	c.1372G>A	p.Glu458Lys	missense	Exon 13 of 14	NP_001136402.1	Q9BZZ5-4
API5	NM_006595.4		c.1372G>A	p.Glu458Lys	missense	Exon 13 of 14	NP_006586.1	Q9BZZ5-2
API5	NM_001142931.2		c.1210G>A	p.Glu404Lys	missense	Exon 12 of 13	NP_001136403.1	Q9BZZ5-5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
API5	ENST00000531273.6	TSL:2 MANE Select	c.1372G>A	p.Glu458Lys	missense	Exon 13 of 14	ENSP00000431391.1	Q9BZZ5-4
API5	ENST00000378852.7	TSL:1	c.1372G>A	p.Glu458Lys	missense	Exon 13 of 14	ENSP00000368129.3	Q9BZZ5-2
API5	ENST00000455725.6	TSL:2	c.1339G>A	p.Glu447Lys	missense	Exon 14 of 15	ENSP00000399341.2	Q9BZZ5-6

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152146

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000283

AC:

AN:

246960

AF XY:

0.0000225

show subpopulations

Gnomad AFR exome

AF:

0.0000620

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:

0.0000535

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000802

AC:

117

AN:

1457984

Hom.:

Cov.:

AF XY:

0.0000662

AC XY:

AN XY:

725186

show subpopulations

African (AFR)

AF:

0.0000301

AC:

AN:

33224

American (AMR)

AF:

0.00

AC:

AN:

43882

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25946

East Asian (EAS)

AF:

0.00

AC:

AN:

39658

South Asian (SAS)

AF:

0.00

AC:

AN:

85346

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53336

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5320

European-Non Finnish (NFE)

AF:

0.0000999

AC:

111

AN:

1111118

Other (OTH)

AF:

0.0000831

AC:

AN:

60154

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152146

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74318

show subpopulations

African (AFR)

AF:

0.0000965

AC:

AN:

41430

American (AMR)

AF:

0.00

AC:

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

68022

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000848

Hom.:

Bravo

AF:

0.0000453

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.42

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.31

CADD

Uncertain

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.036

Eigen

Benign

0.17

Eigen_PC

Uncertain

0.35

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Uncertain

0.96

M_CAP

Benign

0.010

MetaRNN

Benign

0.18

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.6

PhyloP100

9.5

PrimateAI

Uncertain

0.62

PROVEAN

Benign

-0.30

REVEL

Benign

0.14

Sift

Benign

0.53

Sift4G

Benign

0.90

Polyphen

0.47

Vest4

0.51

MVP

0.53

MPC

1.2

ClinPred

0.48

GERP RS

5.2

Varity_R

0.14

gMVP

0.68

Mutation Taster

=30/70

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over