Genetic Variant CEP68:p.Thr203Thr (chr2-65071705-A-G) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_015147.3(CEP68):c.609A>G(p.Thr203Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.227 in 1,613,838 control chromosomes in the GnomAD database, including 43,362 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 0.22 ( 3873 hom., cov: 31)

Exomes 𝑓: 0.23 ( 39489 hom. )

Consequence

CEP68
NM_015147.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.55

Variant links:

Genes affected

CEP68 (HGNC:29076): (centrosomal protein 68) Enables protein domain specific binding activity and protein kinase binding activity. Involved in centriole-centriole cohesion and protein localization to organelle. Located in several cellular components, including centriolar satellite; cytosol; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

CEP68 links:

RAB1A (HGNC:9758): (RAB1A, member RAS oncogene family) This gene encodes a member of the Ras superfamily of GTPases. Members of the gene family cycle between inactive GDP-bound and active GTP-bound forms. This small GTPase controls vesicle traffic from the endoplasmic reticulum to the Golgi apparatus. Multiple alternatively spliced transcript variants have been identified for this gene which encode different protein isoforms. [provided by RefSeq, Oct 2008]

RAB1A links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP7

Synonymous conserved (PhyloP=-2.55 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.321 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEP68	NM_015147.3 link	c.609A>G	p.Thr203Thr	synonymous_variant	Exon 3 of 7	ENST00000377990.7	NP_055962.2	Q76N32-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CEP68	ENST00000377990.7 link	c.609A>G	p.Thr203Thr	synonymous_variant	Exon 3 of 7	1	NM_015147.3	ENSP00000367229.2		Q76N32-1

Frequencies

GnomAD3 genomes

AF:

0.218

AC:

33155

AN:

151958

Hom.:

3859

Cov.:

show subpopulations

Gnomad AFR

AF:

0.169

Gnomad AMI

AF:

0.247

Gnomad AMR

AF:

0.242

Gnomad ASJ

AF:

0.356

Gnomad EAS

AF:

0.334

Gnomad SAS

AF:

0.304

Gnomad FIN

AF:

0.197

Gnomad MID

AF:

0.326

Gnomad NFE

AF:

0.223

Gnomad OTH

AF:

0.250

GnomAD3 exomes

AF:

0.247

AC:

62021

AN:

250818

Hom.:

8038

AF XY:

0.252

AC XY:

34208

AN XY:

135572

show subpopulations

Gnomad AFR exome

AF:

0.167

Gnomad AMR exome

AF:

0.247

Gnomad ASJ exome

AF:

0.366

Gnomad EAS exome

AF:

0.321

Gnomad SAS exome

AF:

0.309

Gnomad FIN exome

AF:

0.201

Gnomad NFE exome

AF:

0.228

Gnomad OTH exome

AF:

0.255

GnomAD4 exome

AF:

0.227

AC:

332431

AN:

1461762

Hom.:

39489

Cov.:

AF XY:

0.231

AC XY:

167817

AN XY:

727186

show subpopulations

Gnomad4 AFR exome

AF:

0.174

Gnomad4 AMR exome

AF:

0.247

Gnomad4 ASJ exome

AF:

0.364

Gnomad4 EAS exome

AF:

0.319

Gnomad4 SAS exome

AF:

0.305

Gnomad4 FIN exome

AF:

0.204

Gnomad4 NFE exome

AF:

0.215

Gnomad4 OTH exome

AF:

0.251

GnomAD4 genome

AF:

0.218

AC:

33204

AN:

152076

Hom.:

3873

Cov.:

AF XY:

0.220

AC XY:

16313

AN XY:

74314

show subpopulations

Gnomad4 AFR

AF:

0.169

Gnomad4 AMR

AF:

0.241

Gnomad4 ASJ

AF:

0.356

Gnomad4 EAS

AF:

0.334

Gnomad4 SAS

AF:

0.306

Gnomad4 FIN

AF:

0.197

Gnomad4 NFE

AF:

0.223

Gnomad4 OTH

AF:

0.258

Alfa

AF:

0.231

Hom.:

5428

Bravo

AF:

0.221

Asia WGS

AF:

0.377

AC:

1311

AN:

3478

EpiCase

AF:

0.233

EpiControl

AF:

0.234

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.047

DANN

Benign

0.43

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over