Variant 3-134558294-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_001353108.3(CEP63):c.1620G>A(p.Arg540=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000719 in 1,613,808 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00053 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00074 ( 3 hom. )

Consequence

CEP63
NM_001353108.3 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.345

Variant links:

Genes affected

CEP63 (HGNC:25815): (centrosomal protein 63) This gene encodes a protein with six coiled-coil domains. The protein is localized to the centrosome, a non-membraneous organelle that functions as the major microtubule-organizing center in animal cells. Several alternatively spliced transcript variants have been found, but their biological validity has not been determined. [provided by RefSeq, Jul 2008]

CEP63 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 3-134558294-G-A is Benign according to our data. Variant chr3-134558294-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 434749.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-134558294-G-A is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=-0.345 with no splicing effect.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000532 (81/152194) while in subpopulation SAS AF= 0.00414 (20/4832). AF 95% confidence interval is 0.00274. There are 0 homozygotes in gnomad4. There are 43 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CEP63	NM_001353108.3 linkuse as main transcript	c.1620G>A	p.Arg540=	synonymous_variant	13/15	ENST00000675561.1	NP_001340037.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CEP63	ENST00000675561.1 linkuse as main transcript	c.1620G>A	p.Arg540=	synonymous_variant	13/15		NM_001353108.3	ENSP00000502085	A1	Q96MT8-1

Frequencies

GnomAD3 genomes

AF:

0.000526

AC:

AN:

152076

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00329

Gnomad AMR

AF:

0.000197

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000735

Gnomad OTH

AF:

0.000957

GnomAD3 exomes

AF:

0.000869

AC:

218

AN:

250982

Hom.:

AF XY:

0.00107

AC XY:

145

AN XY:

135710

show subpopulations

Gnomad AFR exome

AF:

0.000124

Gnomad AMR exome

AF:

0.000434

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00392

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.000661

Gnomad OTH exome

AF:

0.000818

GnomAD4 exome

AF:

0.000738

AC:

1079

AN:

1461614

Hom.:

Cov.:

AF XY:

0.000811

AC XY:

590

AN XY:

727110

show subpopulations

Gnomad4 AFR exome

AF:

0.000149

Gnomad4 AMR exome

AF:

0.000447

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00410

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000551

Gnomad4 OTH exome

AF:

0.000894

GnomAD4 genome

AF:

0.000532

AC:

AN:

152194

Hom.:

Cov.:

AF XY:

0.000578

AC XY:

AN XY:

74394

show subpopulations

Gnomad4 AFR

AF:

0.0000481

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000735

Gnomad4 OTH

AF:

0.000947

Alfa

AF:

0.000674

Hom.:

Bravo

AF:

0.000419

Asia WGS

AF:

0.00202

AC:

AN:

3476

EpiCase

AF:

0.00125

EpiControl

AF:

0.00124

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Mar 01, 2024	CEP63: BP4, BP7 -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Jun 22, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

4.2

DANN

Benign

0.54

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