3-134495139-T-C

Position:

• chr3-134495139-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.-25-157T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.659 in 152,026 control chromosomes in the GnomAD database, including 33,410 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.66 (33410 hom., cov: 32)
• Consequence: CEP63 NM_001353108.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.375

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=-0.84).
• BP6: Variant 3-134495139-T-C is Benign according to our data. Variant chr3-134495139-T-C is described in ClinVar as [Benign]. Clinvar id is 1224910.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	Protein	UniProt
CEP63	NM_001353108.3	c.-25-157T>C		intron_variant		ENST00000675561.1	NP_001340037.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CEP63	ENST00000675561.1	c.-25-157T>C		intron_variant			NM_001353108.3	ENSP00000502085	A1

Frequencies

GnomAD3 genomes AF: 0.659 AC: 100137 AN: 151908 Hom.: 33404 Cov.: 32

Gnomad AFR AF: 0.581

Gnomad AMI AF: 0.478

Gnomad AMR AF: 0.735

Gnomad ASJ AF: 0.667

Gnomad EAS AF: 0.811

Gnomad SAS AF: 0.604

Gnomad FIN AF: 0.737

Gnomad MID AF: 0.658

Gnomad NFE AF: 0.672

Gnomad OTH AF: 0.657

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.659 AC: 100180 AN: 152026 Hom.: 33410 Cov.: 32 AF XY: 0.665 AC XY: 49404 AN XY: 74302

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: 0.737

Gnomad4 NFE AF: 0.672

Gnomad4 OTH AF: 0.656

Alfa AF: 0.583 Hom.: 2363

Bravo AF: 0.659

Asia WGS AF: 0.705 AC: 2451 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

May 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.2
DANN	Benign	0.60

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: rs17694011; hg19: chr3-134213981;