NM_001353108.3:c.1673+12dupT

Variant names:

• chr3-134558353-A-AT
• rs35934324
• NM_001353108.3:c.1673+12dupT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001353108.3(CEP63):​c.1673+12dupT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.31 in 1,572,726 control chromosomes in the GnomAD database, including 78,246 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.32 (7984 hom., cov: 0)
  • Exomes 𝑓: 0.31 (70262 hom.)
• Consequence: CEP63 NM_001353108.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 1.34
• Publications: 3 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 -10 ACMG points.

• BP6: Variant 3-134558353-A-AT is Benign according to our data. Variant chr3-134558353-A-AT is described in ClinVar as Benign. ClinVar VariationId is 210701.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.353 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.1673+12dupT		intron	N/A	NP_001340037.1	Q96MT8-1
	CEP63	NM_025180.5		c.1673+12dupT		intron	N/A	NP_079456.2
	CEP63	NM_001353109.1		c.1535+12dupT		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.1673+12dupT		intron	N/A	ENSP00000502085.1	Q96MT8-1
	CEP63	ENST00000383229.8	TSL:1	c.1468-3018dupT		intron	N/A	ENSP00000372716.3	Q96MT8-2
	CEP63	ENST00000332047.10	TSL:1	c.1330-3018dupT		intron	N/A	ENSP00000328382.5	Q96MT8-3

Frequencies

GnomAD3 genomes AF: 0.318 AC: 48331 AN: 151906 Hom.: 7983 Cov.: 0

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: 0.321

Gnomad FIN AF: 0.263

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.325

Gnomad OTH AF: 0.328

GnomAD2 exomes AF: 0.284 AC: 69824 AN: 245438 AF XY: 0.293

Gnomad AFR exome AF: 0.354

Gnomad AMR exome AF: 0.161

Gnomad ASJ exome AF: 0.305

Gnomad EAS exome AF: 0.169

Gnomad FIN exome AF: 0.258

Gnomad NFE exome AF: 0.320

Gnomad OTH exome AF: 0.294

GnomAD4 exome AF: 0.309 AC: 438710 AN: 1420702 Hom.: 70262 Cov.: 26 AF XY: 0.311 AC XY: 220556 AN XY: 709472

African (AFR) AF: 0.351 AC: 11422 AN: 32558

American (AMR) AF: 0.170 AC: 7566 AN: 44546

Ashkenazi Jewish (ASJ) AF: 0.301 AC: 7770 AN: 25850

East Asian (EAS) AF: 0.192 AC: 7549 AN: 39378

South Asian (SAS) AF: 0.330 AC: 28114 AN: 85260

European-Finnish (FIN) AF: 0.265 AC: 14121 AN: 53274

Middle Eastern (MID) AF: 0.296 AC: 1635 AN: 5522

European-Non Finnish (NFE) AF: 0.319 AC: 342814 AN: 1075334

Other (OTH) AF: 0.300 AC: 17719 AN: 58980

GnomAD4 genome AF: 0.318 AC: 48358 AN: 152024 Hom.: 7984 Cov.: 0 AF XY: 0.312 AC XY: 23168 AN XY: 74294

African (AFR) AF: 0.358 AC: 14812 AN: 41426

American (AMR) AF: 0.253 AC: 3866 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.305 AC: 1058 AN: 3472

East Asian (EAS) AF: 0.178 AC: 923 AN: 5178

South Asian (SAS) AF: 0.321 AC: 1545 AN: 4820

European-Finnish (FIN) AF: 0.263 AC: 2779 AN: 10576

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

European-Non Finnish (NFE) AF: 0.325 AC: 22119 AN: 67966

Other (OTH) AF: 0.327 AC: 691 AN: 2110

Alfa AF: 0.312 Hom.: 1198

Asia WGS AF: 0.242 AC: 841 AN: 3470

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.3
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: rs35934324; hg19: chr3-134277195;