chr3-134517128-G-C

Variant names:

• chr3-134517128-G-C
• rs11919350
• NM_001353108.3:c.222+9842G>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+9842G>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 151,974 control chromosomes in the GnomAD database, including 7,979 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 (7979 hom., cov: 31)
• Consequence: CEP63 NM_001353108.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.50
• Publications: 10 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: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
• 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=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.353 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEP63	NM_001353108.3	c.222+9842G>C		intron_variant	Intron 3 of 14	ENST00000675561.1	NP_001340037.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CEP63	ENST00000675561.1	c.222+9842G>C		intron_variant	Intron 3 of 14		NM_001353108.3	ENSP00000502085.1

Frequencies

GnomAD3 genomes AF: 0.318 AC: 48335 AN: 151856 Hom.: 7978 Cov.: 31

Gnomad AFR AF: 0.358

Gnomad AMI AF: 0.521

Gnomad AMR AF: 0.254

Gnomad ASJ AF: 0.305

Gnomad EAS AF: 0.178

Gnomad SAS AF: 0.322

Gnomad FIN AF: 0.264

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: 48362 AN: 151974 Hom.: 7979 Cov.: 31 AF XY: 0.312 AC XY: 23173 AN XY: 74278

African (AFR) AF: 0.357 AC: 14802 AN: 41414

American (AMR) AF: 0.254 AC: 3874 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.305 AC: 1057 AN: 3468

East Asian (EAS) AF: 0.178 AC: 918 AN: 5164

South Asian (SAS) AF: 0.322 AC: 1549 AN: 4816

European-Finnish (FIN) AF: 0.264 AC: 2782 AN: 10556

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

European-Non Finnish (NFE) AF: 0.326 AC: 22122 AN: 67962

Other (OTH) AF: 0.328 AC: 692 AN: 2108

Alfa AF: 0.198 Hom.: 432

Bravo AF: 0.317

Asia WGS AF: 0.245 AC: 850 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.10
DANN	Benign	0.31
PhyloP100		-1.5
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: rs11919350; hg19: chr3-134235970;