Variant 14-20457358-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001641.4(APEX1):c.807T>C(p.Tyr269Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000777 in 1,614,240 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0035 ( 2 hom., cov: 32)

Exomes 𝑓: 0.00049 ( 3 hom. )

Consequence

APEX1
NM_001641.4 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 1.56

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.67).

BP6

Variant 14-20457358-T-C is Benign according to our data. Variant chr14-20457358-T-C is described in ClinVar as [Benign]. Clinvar id is 715662.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
APEX1	NM_001641.4 linkuse as main transcript	c.807T>C	p.Tyr269Tyr	synonymous_variant	5/5	ENST00000216714.8	NP_001632.2	P27695Q5TZP7
APEX1	NM_001244249.2 linkuse as main transcript	c.807T>C	p.Tyr269Tyr	synonymous_variant	5/5		NP_001231178.1	P27695Q5TZP7
APEX1	NM_080648.3 linkuse as main transcript	c.807T>C	p.Tyr269Tyr	synonymous_variant	5/5		NP_542379.1	P27695Q5TZP7
APEX1	NM_080649.3 linkuse as main transcript	c.807T>C	p.Tyr269Tyr	synonymous_variant	5/5		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.807T>C	p.Tyr269Tyr	synonymous_variant	5/5	1	NM_001641.4	ENSP00000216714.3		P27695

Frequencies

GnomAD3 genomes

AF:

0.00347

AC:

528

AN:

152230

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0118

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000850

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000191

Gnomad OTH

AF:

0.00478

GnomAD3 exomes

AF:

0.000863

AC:

217

AN:

251492

Hom.:

AF XY:

0.000728

AC XY:

AN XY:

135920

show subpopulations

Gnomad AFR exome

AF:

0.0103

Gnomad AMR exome

AF:

0.000463

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.000196

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000176

Gnomad OTH exome

AF:

0.000977

GnomAD4 exome

AF:

0.000495

AC:

723

AN:

1461892

Hom.:

Cov.:

AF XY:

0.000446

AC XY:

324

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.0132

Gnomad4 AMR exome

AF:

0.000626

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000209

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000165

Gnomad4 OTH exome

AF:

0.000679

GnomAD4 genome

AF:

0.00349

AC:

531

AN:

152348

Hom.:

Cov.:

AF XY:

0.00332

AC XY:

247

AN XY:

74506

show subpopulations

Gnomad4 AFR

AF:

0.0119

Gnomad4 AMR

AF:

0.000849

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.000191

Gnomad4 OTH

AF:

0.00473

Alfa

AF:

0.00190

Hom.:

Bravo

AF:

0.00384

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.000178

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Aug 16, 2018

- -

APEX1-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 18, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.67

CADD

Benign

4.3

DANN

Benign

0.63

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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