3-134495200-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001353108.3(CEP63):c.-25-96T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.682 in 874,422 control chromosomes in the GnomAD database, including 205,147 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.66 (33411 hom., cov: 32)
  • Exomes 𝑓: 0.69 (171736 hom.)
• Consequence: CEP63 NM_001353108.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.605

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 3-134495200-T-C is Benign according to our data. Variant chr3-134495200-T-C is described in ClinVar as [Benign]. Clinvar id is 1293011.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.79 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CEP63	NM_001353108.3	c.-25-96T>C		intron_variant		ENST00000675561.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CEP63	ENST00000675561.1	c.-25-96T>C		intron_variant			NM_001353108.3	A1

Frequencies

GnomAD3 genomes AF: 0.659 AC: 100139 AN: 151890 Hom.: 33405 Cov.: 32

Gnomad AFR AF: 0.581

Gnomad AMI AF: 0.478

Gnomad AMR AF: 0.734

Gnomad ASJ AF: 0.667

Gnomad EAS AF: 0.811

Gnomad SAS AF: 0.604

Gnomad FIN AF: 0.736

Gnomad MID AF: 0.658

Gnomad NFE AF: 0.672

Gnomad OTH AF: 0.657

GnomAD4 exome AF: 0.687 AC: 496190 AN: 722416 Hom.: 171736 AF XY: 0.680 AC XY: 262517 AN XY: 385926

Gnomad4 AFR exome AF: 0.591

Gnomad4 AMR exome AF: 0.823

Gnomad4 ASJ exome AF: 0.674

Gnomad4 EAS exome AF: 0.787

Gnomad4 SAS exome AF: 0.599

Gnomad4 FIN exome AF: 0.735

Gnomad4 NFE exome AF: 0.679

Gnomad4 OTH exome AF: 0.687

GnomAD4 genome AF: 0.659 AC: 100182 AN: 152006 Hom.: 33411 Cov.: 32 AF XY: 0.665 AC XY: 49383 AN XY: 74260

Gnomad4 AFR AF: 0.580

Gnomad4 AMR AF: 0.735

Gnomad4 ASJ AF: 0.667

Gnomad4 EAS AF: 0.811

Gnomad4 SAS AF: 0.604

Gnomad4 FIN AF: 0.736

Gnomad4 NFE AF: 0.672

Gnomad4 OTH AF: 0.656

Alfa AF: 0.665 Hom.: 4273

Bravo AF: 0.659

Asia WGS AF: 0.702 AC: 2442 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 10, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	5.8
Dann	Benign	0.82

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: rs62269547; hg19: chr3-134214042;