rs145959811

Variant names:

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_025009.5(CEP135):c.2767G>A(p.Glu923Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00189 in 1,576,822 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0016 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0019 ( 2 hom. )

Consequence

CEP135
NM_025009.5 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:2

Conservation

PhyloP100: 7.08

Variant links:

Genes affected

CEP135 (HGNC:29086): (centrosomal protein 135) This gene encodes a centrosomal protein, which acts as a scaffolding protein during early centriole biogenesis, and is also required for centriole-centriole cohesion during interphase. Mutations in this gene are associated with autosomal recessive primary microcephaly-8. [provided by RefSeq, Jun 2012]

CEP135 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.01546675).

BP6

Variant 4-56011950-G-A is Benign according to our data. Variant chr4-56011950-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 210679.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00156 (237/152282) while in subpopulation NFE AF= 0.00293 (199/68028). AF 95% confidence interval is 0.00259. There are 0 homozygotes in gnomad4. There are 113 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEP135	NM_025009.5 link	c.2767G>A	p.Glu923Lys	missense_variant	Exon 21 of 26	ENST00000257287.5	NP_079285.2	Q66GS9-1
CEP135	XM_006714055.4 link	c.2734G>A	p.Glu912Lys	missense_variant	Exon 21 of 26		XP_006714118.1
CEP135	XM_005265788.5 link	c.1696G>A	p.Glu566Lys	missense_variant	Exon 14 of 19		XP_005265845.1
CEP135	XM_011534412.2 link	c.1237G>A	p.Glu413Lys	missense_variant	Exon 11 of 16		XP_011532714.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CEP135	ENST00000257287.5 link	c.2767G>A	p.Glu923Lys	missense_variant	Exon 21 of 26	1	NM_025009.5	ENSP00000257287.3	Q66GS9-1
CEP135	ENST00000506202.1 link	n.2717G>A		non_coding_transcript_exon_variant	Exon 14 of 19	1
CEP135	ENST00000706801.1 link	n.832G>A		non_coding_transcript_exon_variant	Exon 5 of 10

Frequencies

GnomAD3 genomes

AF:

0.00156

AC:

237

AN:

152164

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000655

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00123

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00292

Gnomad OTH

AF:

0.000957

GnomAD3 exomes

AF:

0.00147

AC:

325

AN:

221644

Hom.:

AF XY:

0.00156

AC XY:

188

AN XY:

120464

show subpopulations

Gnomad AFR exome

AF:

0.000274

Gnomad AMR exome

AF:

0.000593

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000318

Gnomad FIN exome

AF:

0.00155

Gnomad NFE exome

AF:

0.00246

Gnomad OTH exome

AF:

0.00173

GnomAD4 exome

AF:

0.00193

AC:

2746

AN:

1424540

Hom.:

Cov.:

AF XY:

0.00195

AC XY:

1383

AN XY:

708092

show subpopulations

Gnomad4 AFR exome

AF:

0.000287

Gnomad4 AMR exome

AF:

0.000688

Gnomad4 ASJ exome

AF:

0.000161

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000390

Gnomad4 FIN exome

AF:

0.00171

Gnomad4 NFE exome

AF:

0.00226

Gnomad4 OTH exome

AF:

0.00169

GnomAD4 genome

AF:

0.00156

AC:

237

AN:

152282

Hom.:

Cov.:

AF XY:

0.00152

AC XY:

113

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.000241

Gnomad4 AMR

AF:

0.000654

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00123

Gnomad4 NFE

AF:

0.00293

Gnomad4 OTH

AF:

0.000947

Alfa

AF:

0.00210

Hom.:

Bravo

AF:

0.00149

TwinsUK

AF:

0.00297

AC:

ALSPAC

AF:

0.00259

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00314

AC:

ExAC

AF:

0.00174

AC:

211

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:2

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Apr 04, 2014

Genetic Services Laboratory, University of Chicago

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

CEP135-related disorder

Benign:1

Apr 20, 2022

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided

Benign:1

Feb 01, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.53

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.30

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.17

Eigen

Pathogenic

0.83

Eigen_PC

Pathogenic

0.82

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.95

M_CAP

Benign

0.043

MetaRNN

Benign

0.015

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.4

PrimateAI

Uncertain

0.69

PROVEAN

Uncertain

-3.0

REVEL

Benign

0.22

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.028

Polyphen

1.0

Vest4

0.26

MVP

0.75

MPC

0.38

ClinPred

0.046

GERP RS

5.7

Varity_R

0.69

gMVP

0.32

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

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over