rs11927068

Variant names:

• chr3-134547479-A-G
• rs11927068
• NM_001353108.3:c.1067+7A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001353108.3(CEP63):​c.1067+7A>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.314 in 1,610,868 control chromosomes in the GnomAD database, including 81,131 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.32 (7997 hom., cov: 30)
  • Exomes 𝑓: 0.31 (73134 hom.)
• Consequence: CEP63 NM_001353108.3 splice_region, intron
• Scores: Splicing: ADA: 0.00007666
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 1.33
• Publications: 13 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: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
• autosomal recessive primary microcephaly

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000288700 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BP6: Variant 3-134547479-A-G is Benign according to our data. Variant chr3-134547479-A-G is described in ClinVar as Benign. ClinVar VariationId is 128706.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.354 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.1067+7A>G		splice_region intron	N/A	NP_001340037.1	Q96MT8-1
	CEP63	NM_025180.5		c.1067+7A>G		splice_region intron	N/A	NP_079456.2
	CEP63	NM_001353109.1		c.929+1191A>G		intron	N/A	NP_001340038.1	A0A804HIX3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP63	ENST00000675561.1	MANE Select	c.1067+7A>G		splice_region intron	N/A	ENSP00000502085.1	Q96MT8-1
	CEP63	ENST00000383229.8	TSL:1	c.1067+7A>G		splice_region intron	N/A	ENSP00000372716.3	Q96MT8-2
	CEP63	ENST00000332047.10	TSL:1	c.929+1191A>G		intron	N/A	ENSP00000328382.5	Q96MT8-3

Frequencies

GnomAD3 genomes AF: 0.319 AC: 48398 AN: 151786 Hom.: 7996 Cov.: 30

Gnomad AFR AF: 0.359

Gnomad AMI AF: 0.521

Gnomad AMR AF: 0.254

Gnomad ASJ AF: 0.306

Gnomad EAS AF: 0.179

Gnomad SAS AF: 0.322

Gnomad FIN AF: 0.264

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.326

Gnomad OTH AF: 0.329

GnomAD2 exomes AF: 0.287 AC: 71958 AN: 250730 AF XY: 0.295

Gnomad AFR exome AF: 0.358

Gnomad AMR exome AF: 0.162

Gnomad ASJ exome AF: 0.306

Gnomad EAS exome AF: 0.170

Gnomad FIN exome AF: 0.259

Gnomad NFE exome AF: 0.323

Gnomad OTH exome AF: 0.297

GnomAD4 exome AF: 0.314 AC: 457438 AN: 1458964 Hom.: 73134 Cov.: 33 AF XY: 0.315 AC XY: 228791 AN XY: 726026

African (AFR) AF: 0.355 AC: 11864 AN: 33416

American (AMR) AF: 0.171 AC: 7632 AN: 44704

Ashkenazi Jewish (ASJ) AF: 0.302 AC: 7889 AN: 26112

East Asian (EAS) AF: 0.192 AC: 7634 AN: 39672

South Asian (SAS) AF: 0.331 AC: 28562 AN: 86194

European-Finnish (FIN) AF: 0.266 AC: 14147 AN: 53230

Middle Eastern (MID) AF: 0.300 AC: 1727 AN: 5764

European-Non Finnish (NFE) AF: 0.324 AC: 359626 AN: 1109560

Other (OTH) AF: 0.304 AC: 18357 AN: 60312

GnomAD4 genome AF: 0.319 AC: 48425 AN: 151904 Hom.: 7997 Cov.: 30 AF XY: 0.313 AC XY: 23197 AN XY: 74208

African (AFR) AF: 0.359 AC: 14861 AN: 41432

American (AMR) AF: 0.254 AC: 3868 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.306 AC: 1058 AN: 3462

East Asian (EAS) AF: 0.179 AC: 924 AN: 5160

South Asian (SAS) AF: 0.322 AC: 1547 AN: 4810

European-Finnish (FIN) AF: 0.264 AC: 2781 AN: 10548

Middle Eastern (MID) AF: 0.313 AC: 92 AN: 294

European-Non Finnish (NFE) AF: 0.326 AC: 22127 AN: 67920

Other (OTH) AF: 0.329 AC: 694 AN: 2112

Alfa AF: 0.319 Hom.: 3472

Bravo AF: 0.317

Asia WGS AF: 0.245 AC: 851 AN: 3478

EpiCase AF: 0.329

EpiControl AF: 0.329

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	2	not specified (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	7.3
DANN	Benign	0.66
PhyloP100		1.3
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000077
dbscSNV1_RF	Benign	0.0
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: rs11927068; hg19: chr3-134266321; COSMIC: COSV59675037; COSMIC: COSV59675037;