Variant 14-20456680-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001641.4(APEX1):c.259G>C(p.Glu87Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,802 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as not provided (no stars).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

APEX1
NM_001641.4 missense

Scores

Clinical Significance

not provided no classification provided O:1

Conservation

PhyloP100: 9.48

Variant links:

Genes affected

APEX1 (HGNC:587): (apurinic/apyrimidinic endodeoxyribonuclease 1) The APEX gene encodes the major AP endonuclease in human cells. It encodes the APEX endonuclease, a DNA repair enzyme with apurinic/apyrimidinic (AP) activity. Such AP activity sites occur frequently in DNA molecules by spontaneous hydrolysis, by DNA damaging agents or by DNA glycosylases that remove specific abnormal bases. The AP sites are the most frequent pre-mutagenic lesions that can prevent normal DNA replication. Splice variants have been found for this gene; all encode the same protein. Disruptions in the biological functions related to APEX are associated with many various malignancies and neurodegenerative diseases.[provided by RefSeq, Dec 2019]

APEX1 links:

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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	Protein	UniProt
APEX1	NM_001641.4 linkuse as main transcript	c.259G>C	p.Glu87Gln	missense_variant	4/5	ENST00000216714.8	NP_001632.2	P27695Q5TZP7
APEX1	NM_001244249.2 linkuse as main transcript	c.259G>C	p.Glu87Gln	missense_variant	4/5		NP_001231178.1	P27695Q5TZP7
APEX1	NM_080648.3 linkuse as main transcript	c.259G>C	p.Glu87Gln	missense_variant	4/5		NP_542379.1	P27695Q5TZP7
APEX1	NM_080649.3 linkuse as main transcript	c.259G>C	p.Glu87Gln	missense_variant	4/5		NP_542380.1	P27695Q5TZP7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
APEX1	ENST00000216714.8 linkuse as main transcript	c.259G>C	p.Glu87Gln	missense_variant	4/5	1	NM_001641.4	ENSP00000216714.3		P27695

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000795

AC:

AN:

251478

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135918

show subpopulations

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 SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461802

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727214

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

LINK: link

Submissions by phenotype

Head and neck cancer

Other:1

not provided, no classification provided

research

Cancer Biology Lab, VIT University

Oct 12, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.80

BayesDel_addAF

Uncertain

0.092

BayesDel_noAF

Uncertain

0.080

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.42

T;T;T;T;T;T;.;T;T;.

Eigen

Uncertain

0.59

Eigen_PC

Pathogenic

0.68

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.96

.;.;D;D;D;D;D;D;D;D

M_CAP

Benign

0.054

MetaRNN

Uncertain

0.69

D;D;D;D;D;D;D;D;D;D

MetaSVM

Benign

-0.53

MutationAssessor

Benign

1.8

L;L;.;.;L;.;.;.;.;.

PrimateAI

Uncertain

0.54

PROVEAN

Uncertain

-2.9

D;D;D;D;D;D;D;D;D;D

REVEL

Uncertain

0.62

Sift

Uncertain

0.016

D;D;T;D;D;D;D;D;D;D

Sift4G

Benign

0.28

T;T;T;D;T;D;T;T;T;D

Polyphen

1.0

D;D;.;.;D;.;.;.;.;.

Vest4

0.69

MutPred

0.52

Gain of catalytic residue at E87 (P = 0.0016);Gain of catalytic residue at E87 (P = 0.0016);Gain of catalytic residue at E87 (P = 0.0016);Gain of catalytic residue at E87 (P = 0.0016);Gain of catalytic residue at E87 (P = 0.0016);Gain of catalytic residue at E87 (P = 0.0016);Gain of catalytic residue at E87 (P = 0.0016);Gain of catalytic residue at E87 (P = 0.0016);.;.;

MVP

0.87

MPC

0.71

ClinPred

0.75

GERP RS

5.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.8

Varity_R

0.93

gMVP

0.83

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over