rs140668390

chr3-134558294-G-Achr3-134558294-G-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

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
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.345

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]

ACMG classification

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. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome at 2 AR gene

Transcripts

RefSeq

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

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CEP63	ENST00000675561.1	c.1620G>A	p.Arg540=	synonymous_variant	13/15		NM_001353108.3	A1

Frequencies

GnomAD3 genomes AF: 0.000526 AC: 80 AN: 152076 Hom.: 0 Cov.: 31

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.: 2 AF XY: 0.00107 AC XY: 145 AN XY: 135710

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.: 3 Cov.: 31 AF XY: 0.000811 AC XY: 590 AN XY: 727110

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: 81 AN: 152194 Hom.: 0 Cov.: 31 AF XY: 0.000578 AC XY: 43 AN XY: 74394

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.: 0

Bravo AF: 0.000419

Asia WGS AF: 0.00202 AC: 7 AN: 3476

EpiCase AF: 0.00125

EpiControl AF: 0.00124

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 29, 2024	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Mar 01, 2024	CEP63: BP4, BP7 -

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

Other links and lift over

dbSNP: rs140668390; hg19: chr3-134277136;