Variant chrX-55001565-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_014481.4(APEX2):c.177C>T(p.Pro59Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00806 in 1,204,475 control chromosomes in the GnomAD database, including 33 homozygotes. There are 3,058 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0063 ( 2 hom., 217 hem., cov: 23)

Exomes 𝑓: 0.0082 ( 31 hom. 2841 hem. )

Consequence

APEX2
NM_014481.4 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.552

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:

APEX2 (HGNC:):

APEX2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.73).

BP6

Variant X-55001565-C-T is Benign according to our data. Variant chrX-55001565-C-T is described in ClinVar as [Benign]. Clinvar id is 718857.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-55001565-C-T is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=-0.552 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
APEX2	NM_014481.4 linkuse as main transcript	c.177C>T	p.Pro59Pro	synonymous_variant	2/6	ENST00000374987.4	NP_055296.2	Q9UBZ4E5KN95
APEX2	NM_001271748.2 linkuse as main transcript	c.-156C>T		5_prime_UTR_variant	2/5		NP_001258677.1	B7ZA71B4DWI9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
APEX2	ENST00000374987.4 linkuse as main transcript	c.177C>T	p.Pro59Pro	synonymous_variant	2/6	1	NM_014481.4	ENSP00000364126.3		Q9UBZ4
APEX2	ENST00000471758.1 linkuse as main transcript	n.207C>T		non_coding_transcript_exon_variant	2/5	2

Frequencies

GnomAD3 genomes

AF:

0.00626

AC:

696

AN:

111123

Hom.:

Cov.:

AF XY:

0.00652

AC XY:

217

AN XY:

33301

show subpopulations

Gnomad AFR

AF:

0.000919

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000860

Gnomad ASJ

AF:

0.00189

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0208

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00992

Gnomad OTH

AF:

0.00331

GnomAD3 exomes

AF:

0.00640

AC:

1089

AN:

170201

Hom.:

AF XY:

0.00541

AC XY:

302

AN XY:

55871

show subpopulations

Gnomad AFR exome

AF:

0.00186

Gnomad AMR exome

AF:

0.00131

Gnomad ASJ exome

AF:

0.00125

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0207

Gnomad NFE exome

AF:

0.00914

Gnomad OTH exome

AF:

0.00471

GnomAD4 exome

AF:

0.00824

AC:

9014

AN:

1093300

Hom.:

Cov.:

AF XY:

0.00791

AC XY:

2841

AN XY:

359180

show subpopulations

Gnomad4 AFR exome

AF:

0.00141

Gnomad4 AMR exome

AF:

0.00153

Gnomad4 ASJ exome

AF:

0.00182

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000754

Gnomad4 FIN exome

AF:

0.0187

Gnomad4 NFE exome

AF:

0.00937

Gnomad4 OTH exome

AF:

0.00573

GnomAD4 genome

AF:

0.00626

AC:

696

AN:

111175

Hom.:

Cov.:

AF XY:

0.00650

AC XY:

217

AN XY:

33363

show subpopulations

Gnomad4 AFR

AF:

0.000917

Gnomad4 AMR

AF:

0.000859

Gnomad4 ASJ

AF:

0.00189

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0208

Gnomad4 NFE

AF:

0.00992

Gnomad4 OTH

AF:

0.00327

Alfa

AF:

0.00863

Hom.:

Bravo

AF:

0.00435

ClinVar

Significance: Benign

Submissions summary: Benign:1

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 09, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

5.4

DANN

Benign

0.77

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