NM_001353108.3:c.63T>C

Variant names:

• chr3-134507127-T-C
• rs9827878
• NM_001353108.3:c.63T>C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001353108.3(CEP63):​c.63T>C​(p.Cys21Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.165 in 1,612,436 control chromosomes in the GnomAD database, including 22,464 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.16 (1922 hom., cov: 31)
  • Exomes 𝑓: 0.17 (20542 hom.)
• Consequence: CEP63 NM_001353108.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 1.66
• Publications: 18 publications found

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]

CEP63 Gene-Disease associations (from GenCC):

• Seckel syndrome 6

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

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000288700 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP6: Variant 3-134507127-T-C is Benign according to our data. Variant chr3-134507127-T-C is described in ClinVar as Benign. ClinVar VariationId is 128712.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.65 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.194 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001353108.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP63	NM_001353108.3	MANE Select	c.63T>C	p.Cys21Cys	synonymous	Exon 3 of 15	NP_001340037.1	Q96MT8-1
	CEP63	NM_025180.5		c.63T>C	p.Cys21Cys	synonymous	Exon 4 of 16	NP_079456.2
	CEP63	NM_001353109.1		c.63T>C	p.Cys21Cys	synonymous	Exon 3 of 14	NP_001340038.1	A0A804HIX3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP63	ENST00000675561.1	MANE Select	c.63T>C	p.Cys21Cys	synonymous	Exon 3 of 15	ENSP00000502085.1	Q96MT8-1
	CEP63	ENST00000383229.8	TSL:1	c.63T>C	p.Cys21Cys	synonymous	Exon 3 of 13	ENSP00000372716.3	Q96MT8-2
	CEP63	ENST00000332047.10	TSL:1	c.63T>C	p.Cys21Cys	synonymous	Exon 3 of 12	ENSP00000328382.5	Q96MT8-3

Frequencies

GnomAD3 genomes AF: 0.157 AC: 23833 AN: 151820 Hom.: 1919 Cov.: 31

Gnomad AFR AF: 0.128

Gnomad AMI AF: 0.108

Gnomad AMR AF: 0.148

Gnomad ASJ AF: 0.105

Gnomad EAS AF: 0.204

Gnomad SAS AF: 0.183

Gnomad FIN AF: 0.224

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.165

Gnomad OTH AF: 0.142

GnomAD2 exomes AF: 0.171 AC: 42982 AN: 251218 AF XY: 0.169

Gnomad AFR exome AF: 0.126

Gnomad AMR exome AF: 0.167

Gnomad ASJ exome AF: 0.102

Gnomad EAS exome AF: 0.217

Gnomad FIN exome AF: 0.231

Gnomad NFE exome AF: 0.166

Gnomad OTH exome AF: 0.153

GnomAD4 exome AF: 0.166 AC: 241908 AN: 1460498 Hom.: 20542 Cov.: 32 AF XY: 0.166 AC XY: 120377 AN XY: 726608

African (AFR) AF: 0.129 AC: 4308 AN: 33442

American (AMR) AF: 0.162 AC: 7248 AN: 44698

Ashkenazi Jewish (ASJ) AF: 0.100 AC: 2618 AN: 26110

East Asian (EAS) AF: 0.181 AC: 7161 AN: 39614

South Asian (SAS) AF: 0.176 AC: 15206 AN: 86198

European-Finnish (FIN) AF: 0.234 AC: 12477 AN: 53396

Middle Eastern (MID) AF: 0.123 AC: 710 AN: 5762

European-Non Finnish (NFE) AF: 0.164 AC: 182464 AN: 1110916

Other (OTH) AF: 0.161 AC: 9716 AN: 60362

GnomAD4 genome AF: 0.157 AC: 23840 AN: 151938 Hom.: 1922 Cov.: 31 AF XY: 0.159 AC XY: 11788 AN XY: 74222

African (AFR) AF: 0.128 AC: 5304 AN: 41454

American (AMR) AF: 0.149 AC: 2273 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.105 AC: 365 AN: 3472

East Asian (EAS) AF: 0.204 AC: 1052 AN: 5160

South Asian (SAS) AF: 0.182 AC: 876 AN: 4808

European-Finnish (FIN) AF: 0.224 AC: 2361 AN: 10518

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.165 AC: 11185 AN: 67964

Other (OTH) AF: 0.140 AC: 296 AN: 2108

Alfa AF: 0.160 Hom.: 7795

Bravo AF: 0.152

Asia WGS AF: 0.210 AC: 731 AN: 3478

EpiCase AF: 0.158

EpiControl AF: 0.152

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	9.6
DANN	Benign	0.86
PhyloP100		1.7
Mutation Taster		=96/4	polymorphism (auto)

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

Other links and lift over

dbSNP: rs9827878; hg19: chr3-134225969; COSMIC: COSV59676362; COSMIC: COSV59676362;