Variant X-55006683-C-T 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_014481.4(APEX2):c.805C>T(p.His269Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000392 in 1,165,491 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 195 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.00026 ( 0 hom., 10 hem., cov: 23)

Exomes 𝑓: 0.00041 ( 0 hom. 185 hem. )

Consequence

APEX2
NM_014481.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.02

Variant links:

Genes affected

APEX2 (HGNC:17889): (apurinic/apyrimidinic endodeoxyribonuclease 2) Apurinic/apyrimidinic (AP) sites occur frequently in DNA molecules by spontaneous hydrolysis, by DNA damaging agents or by DNA glycosylases that remove specific abnormal bases. AP sites are pre-mutagenic lesions that can prevent normal DNA replication so the cell contains systems to identify and repair such sites. Class II AP endonucleases cleave the phosphodiester backbone 5' to the AP site. This gene encodes a protein shown to have a weak class II AP endonuclease activity. Most of the encoded protein is located in the nucleus but some is also present in mitochondria. This protein may play an important role in both nuclear and mitochondrial base excision repair. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Nov 2012]

APEX2 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 (MetaRNN=0.00992167).

BP6

Variant X-55006683-C-T is Benign according to our data. Variant chrX-55006683-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2660688.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAd4 at 10 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
APEX2	NM_014481.4 linkuse as main transcript	c.805C>T	p.His269Tyr	missense_variant	6/6	ENST00000374987.4
APEX2	NM_001271748.2 linkuse as main transcript	c.292C>T	p.His98Tyr	missense_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
APEX2	ENST00000374987.4 linkuse as main transcript	c.805C>T	p.His269Tyr	missense_variant	6/6	1	NM_014481.4	P1
APEX2	ENST00000471758.1 linkuse as main transcript	n.654C>T		non_coding_transcript_exon_variant	5/5	2

Frequencies

GnomAD3 genomes

AF:

0.000258

AC:

AN:

112245

Hom.:

Cov.:

AF XY:

0.000291

AC XY:

AN XY:

34389

show subpopulations

Gnomad AFR

AF:

0.0000324

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00558

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000207

Gnomad OTH

AF:

0.00133

GnomAD3 exomes

AF:

0.000490

AC:

AN:

138647

Hom.:

AF XY:

0.000614

AC XY:

AN XY:

37453

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000245

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00501

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000223

Gnomad OTH exome

AF:

0.000895

GnomAD4 exome

AF:

0.000406

AC:

428

AN:

1053190

Hom.:

Cov.:

AF XY:

0.000551

AC XY:

185

AN XY:

335570

show subpopulations

Gnomad4 AFR exome

AF:

0.0000397

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00555

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000161

Gnomad4 OTH exome

AF:

0.000363

GnomAD4 genome

AF:

0.000258

AC:

AN:

112301

Hom.:

Cov.:

AF XY:

0.000290

AC XY:

AN XY:

34455

show subpopulations

Gnomad4 AFR

AF:

0.0000323

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00560

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000207

Gnomad4 OTH

AF:

0.00131

Alfa

AF:

0.000255

Hom.:

Bravo

AF:

0.000117

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000297

AC:

ExAC

AF:

0.000803

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Mar 01, 2023

APEX2: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.61

CADD

Benign

DANN

Benign

0.92

DEOGEN2

Benign

0.29

FATHMM_MKL

Uncertain

0.77

LIST_S2

Benign

0.60

M_CAP

Pathogenic

0.43

MetaRNN

Benign

0.0099

MetaSVM

Benign

-0.96

MutationAssessor

Benign

1.3

MutationTaster

Benign

0.89

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-1.3

REVEL

Benign

0.12

Sift

Benign

0.091

Sift4G

Uncertain

0.020

Polyphen

0.75

Vest4

0.035

MVP

0.49

MPC

0.17

ClinPred

0.042

GERP RS

1.6

Varity_R

0.11

gMVP

0.37

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