3-134514250-A-G

Variant names:

• chr3-134514250-A-G
• rs10935120
• NM_001353108.3:c.222+6964A>G

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+6964A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.634 in 152,068 control chromosomes in the GnomAD database, including 31,257 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 0.63 (31257 hom., cov: 32)
• Consequence: CEP63 NM_001353108.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.478
• Publications: 50 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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.791 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP63	NM_001353108.3	MANE Select	c.222+6964A>G		intron	N/A	NP_001340037.1
	CEP63	NM_025180.5		c.222+6964A>G		intron	N/A	NP_079456.2
	CEP63	NM_001353109.1		c.222+6964A>G		intron	N/A	NP_001340038.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP63	ENST00000675561.1	MANE Select	c.222+6964A>G		intron	N/A	ENSP00000502085.1
	CEP63	ENST00000383229.8	TSL:1	c.222+6964A>G		intron	N/A	ENSP00000372716.3
	CEP63	ENST00000332047.10	TSL:1	c.222+6964A>G		intron	N/A	ENSP00000328382.5

Frequencies

GnomAD3 genomes AF: 0.634 AC: 96337 AN: 151950 Hom.: 31255 Cov.: 32

Gnomad AFR AF: 0.494

Gnomad AMI AF: 0.472

Gnomad AMR AF: 0.723

Gnomad ASJ AF: 0.668

Gnomad EAS AF: 0.811

Gnomad SAS AF: 0.604

Gnomad FIN AF: 0.738

Gnomad MID AF: 0.652

Gnomad NFE AF: 0.672

Gnomad OTH AF: 0.636

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

GnomAD4 genome AF: 0.634 AC: 96362 AN: 152068 Hom.: 31257 Cov.: 32 AF XY: 0.641 AC XY: 47620 AN XY: 74334

African (AFR) AF: 0.493 AC: 20442 AN: 41476

American (AMR) AF: 0.724 AC: 11051 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.668 AC: 2317 AN: 3470

East Asian (EAS) AF: 0.811 AC: 4198 AN: 5176

South Asian (SAS) AF: 0.604 AC: 2917 AN: 4830

European-Finnish (FIN) AF: 0.738 AC: 7787 AN: 10552

Middle Eastern (MID) AF: 0.643 AC: 189 AN: 294

European-Non Finnish (NFE) AF: 0.672 AC: 45690 AN: 67978

Other (OTH) AF: 0.636 AC: 1343 AN: 2112

Alfa AF: 0.662 Hom.: 79921

Bravo AF: 0.630

Asia WGS AF: 0.693 AC: 2406 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	11
DANN	Benign	0.65
PhyloP100		-0.48
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: rs10935120; hg19: chr3-134233092;