rs9968172

Positions:

• chr3-134512409-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001353108.3(CEP63):​c.222+5123T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.318 in 152,136 control chromosomes in the GnomAD database, including 7,999 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.32 (7999 hom., cov: 33)
• Consequence: CEP63 NM_001353108.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.09

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.354 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CEP63	NM_001353108.3	c.222+5123T>C		intron_variant		ENST00000675561.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CEP63	ENST00000675561.1	c.222+5123T>C		intron_variant			NM_001353108.3	A1

Frequencies

GnomAD3 genomes AF: 0.319 AC: 48423 AN: 152018 Hom.: 7998 Cov.: 33

Gnomad AFR AF: 0.359

Gnomad AMI AF: 0.521

Gnomad AMR AF: 0.254

Gnomad ASJ AF: 0.305

Gnomad EAS AF: 0.179

Gnomad SAS AF: 0.322

Gnomad FIN AF: 0.263

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.326

Gnomad OTH AF: 0.328

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

GnomAD4 genome AF: 0.318 AC: 48450 AN: 152136 Hom.: 7999 Cov.: 33 AF XY: 0.312 AC XY: 23232 AN XY: 74384

Gnomad4 AFR AF: 0.358

Gnomad4 AMR AF: 0.254

Gnomad4 ASJ AF: 0.305

Gnomad4 EAS AF: 0.179

Gnomad4 SAS AF: 0.322

Gnomad4 FIN AF: 0.263

Gnomad4 NFE AF: 0.326

Gnomad4 OTH AF: 0.328

Alfa AF: 0.317 Hom.: 1519

Bravo AF: 0.317

Asia WGS AF: 0.245 AC: 851 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	5.5
DANN	Benign	0.74

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: rs9968172; hg19: chr3-134231251;