NM_001353108.3:c.45-266G>A

Variant names:

• chr3-134506843-G-A
• rs4974478
• NM_001353108.3:c.45-266G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001353108.3(CEP63):​c.45-266G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.662 in 149,044 control chromosomes in the GnomAD database, including 32,908 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.66 (32908 hom., cov: 24)
• Consequence: CEP63 NM_001353108.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.45
• Publications: 5 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BP6: Variant 3-134506843-G-A is Benign according to our data. Variant chr3-134506843-G-A is described in ClinVar as Benign. ClinVar VariationId is 1274368.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.794 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.45-266G>A		intron	N/A	NP_001340037.1	Q96MT8-1
	CEP63	NM_025180.5		c.45-266G>A		intron	N/A	NP_079456.2
	CEP63	NM_001353109.1		c.45-266G>A		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.45-266G>A		intron	N/A	ENSP00000502085.1	Q96MT8-1
	CEP63	ENST00000383229.8	TSL:1	c.45-266G>A		intron	N/A	ENSP00000372716.3	Q96MT8-2
	CEP63	ENST00000332047.10	TSL:1	c.45-266G>A		intron	N/A	ENSP00000328382.5	Q96MT8-3

Frequencies

GnomAD3 genomes AF: 0.662 AC: 98610 AN: 148942 Hom.: 32901 Cov.: 24

Gnomad AFR AF: 0.587

Gnomad AMI AF: 0.481

Gnomad AMR AF: 0.738

Gnomad ASJ AF: 0.668

Gnomad EAS AF: 0.815

Gnomad SAS AF: 0.611

Gnomad FIN AF: 0.741

Gnomad MID AF: 0.661

Gnomad NFE AF: 0.673

Gnomad OTH AF: 0.662

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

GnomAD4 genome AF: 0.662 AC: 98654 AN: 149044 Hom.: 32908 Cov.: 24 AF XY: 0.668 AC XY: 48461 AN XY: 72544

African (AFR) AF: 0.586 AC: 23559 AN: 40192

American (AMR) AF: 0.739 AC: 11046 AN: 14952

Ashkenazi Jewish (ASJ) AF: 0.668 AC: 2314 AN: 3466

East Asian (EAS) AF: 0.815 AC: 4073 AN: 5000

South Asian (SAS) AF: 0.611 AC: 2842 AN: 4648

European-Finnish (FIN) AF: 0.741 AC: 7364 AN: 9940

Middle Eastern (MID) AF: 0.652 AC: 184 AN: 282

European-Non Finnish (NFE) AF: 0.673 AC: 45474 AN: 67602

Other (OTH) AF: 0.662 AC: 1368 AN: 2068

Alfa AF: 0.666 Hom.: 4246

Bravo AF: 0.660

Asia WGS AF: 0.705 AC: 2451 AN: 3474

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.11
DANN	Benign	0.55
PhyloP100		-2.5
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: rs4974478; hg19: chr3-134225685;