chr3-134695377-C-A

Variant names:

• chr3-134695377-C-A
• rs1984630
• ENST00000460895.5:n.74+79939C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000460895.5(ENSG00000288700):​n.74+79939C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.455 in 152,062 control chromosomes in the GnomAD database, including 16,420 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 0.45 (16420 hom., cov: 33)
• Consequence: ENSG00000288700 ENST00000460895.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.82
• Publications: 6 publications found

Genes affected

ENSG00000288700 (HGNC:):

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 Gene-Disease associations (from GenCC):

• Seckel syndrome 6

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
• autosomal recessive primary microcephaly

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.673 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEP63	XR_007095731.1	n.1927+79939C>A		intron_variant	Intron 13 of 13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000288700	ENST00000460895.5	n.74+79939C>A		intron_variant	Intron 1 of 3	3
ENSG00000288700	ENST00000467708.2	n.362-60282C>A		intron_variant	Intron 2 of 3	4

Frequencies

GnomAD3 genomes AF: 0.455 AC: 69085 AN: 151946 Hom.: 16402 Cov.: 33

Gnomad AFR AF: 0.320

Gnomad AMI AF: 0.626

Gnomad AMR AF: 0.457

Gnomad ASJ AF: 0.494

Gnomad EAS AF: 0.692

Gnomad SAS AF: 0.631

Gnomad FIN AF: 0.539

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.488

Gnomad OTH AF: 0.463

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

GnomAD4 genome AF: 0.455 AC: 69116 AN: 152062 Hom.: 16420 Cov.: 33 AF XY: 0.463 AC XY: 34376 AN XY: 74320

African (AFR) AF: 0.320 AC: 13271 AN: 41468

American (AMR) AF: 0.457 AC: 6990 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.494 AC: 1713 AN: 3468

East Asian (EAS) AF: 0.692 AC: 3569 AN: 5156

South Asian (SAS) AF: 0.631 AC: 3045 AN: 4826

European-Finnish (FIN) AF: 0.539 AC: 5705 AN: 10582

Middle Eastern (MID) AF: 0.418 AC: 123 AN: 294

European-Non Finnish (NFE) AF: 0.488 AC: 33141 AN: 67956

Other (OTH) AF: 0.467 AC: 988 AN: 2114

Alfa AF: 0.473 Hom.: 10330

Bravo AF: 0.437

Asia WGS AF: 0.630 AC: 2189 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	0.69
DANN	Benign	0.81
PhyloP100		-2.8

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1984630; hg19: chr3-134414219;