chr3-134514396-G-T

Variant names:

• chr3-134514396-G-T
• rs7619451
• NM_001353108.3:c.222+7110G>T

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+7110G>T 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 151,958 control chromosomes in the GnomAD database, including 7,965 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 (7965 hom., cov: 32)
• Consequence: CEP63 NM_001353108.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.77
• Publications: 18 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.352 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEP63	NM_001353108.3	c.222+7110G>T		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+7110G>T		intron_variant	Intron 3 of 14		NM_001353108.3	ENSP00000502085.1

Frequencies

GnomAD3 genomes AF: 0.318 AC: 48312 AN: 151840 Hom.: 7964 Cov.: 32

Gnomad AFR AF: 0.357

Gnomad AMI AF: 0.519

Gnomad AMR AF: 0.254

Gnomad ASJ AF: 0.304

Gnomad EAS AF: 0.179

Gnomad SAS AF: 0.323

Gnomad FIN AF: 0.262

Gnomad MID AF: 0.304

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: 48339 AN: 151958 Hom.: 7965 Cov.: 32 AF XY: 0.312 AC XY: 23171 AN XY: 74294

African (AFR) AF: 0.357 AC: 14791 AN: 41424

American (AMR) AF: 0.253 AC: 3868 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.304 AC: 1056 AN: 3468

East Asian (EAS) AF: 0.179 AC: 926 AN: 5168

South Asian (SAS) AF: 0.322 AC: 1555 AN: 4824

European-Finnish (FIN) AF: 0.262 AC: 2756 AN: 10512

Middle Eastern (MID) AF: 0.310 AC: 91 AN: 294

European-Non Finnish (NFE) AF: 0.326 AC: 22130 AN: 67966

Other (OTH) AF: 0.328 AC: 694 AN: 2116

Alfa AF: 0.327 Hom.: 1334

Bravo AF: 0.317

Asia WGS AF: 0.244 AC: 848 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.2
DANN	Benign	0.52
PhyloP100		1.8
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: rs7619451; hg19: chr3-134233238;