rs9968172

Variant names:

• chr3-134512409-T-C
• rs9968172
• NM_001353108.3:c.222+5123T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 21 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 -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.

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.222+5123T>C		intron	N/A	NP_001340037.1	Q96MT8-1
	CEP63	NM_025180.5		c.222+5123T>C		intron	N/A	NP_079456.2
	CEP63	NM_001353109.1		c.222+5123T>C		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.222+5123T>C		intron	N/A	ENSP00000502085.1	Q96MT8-1
	CEP63	ENST00000383229.8	TSL:1	c.222+5123T>C		intron	N/A	ENSP00000372716.3	Q96MT8-2
	CEP63	ENST00000332047.10	TSL:1	c.222+5123T>C		intron	N/A	ENSP00000328382.5	Q96MT8-3

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

African (AFR) AF: 0.358 AC: 14863 AN: 41478

American (AMR) AF: 0.254 AC: 3877 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.305 AC: 1056 AN: 3466

East Asian (EAS) AF: 0.179 AC: 928 AN: 5182

South Asian (SAS) AF: 0.322 AC: 1552 AN: 4824

European-Finnish (FIN) AF: 0.263 AC: 2785 AN: 10598

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

European-Non Finnish (NFE) AF: 0.326 AC: 22134 AN: 67990

Other (OTH) AF: 0.328 AC: 691 AN: 2108

Alfa AF: 0.317 Hom.: 1559

Bravo AF: 0.317

Asia WGS AF: 0.245 AC: 851 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	5.5
DANN	Benign	0.74
PhyloP100		1.1
Mutation Taster		=100/0	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: rs9968172; hg19: chr3-134231251;