rs77591659

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_025009.5(CEP135):c.335G>A(p.Arg112His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0353 in 1,600,192 control chromosomes in the GnomAD database, including 1,177 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.027 ( 69 hom., cov: 33)

Exomes 𝑓: 0.036 ( 1108 hom. )

Consequence

CEP135
NM_025009.5 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 2.08

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:

LOC124900705 (HGNC:):

LOC124900705 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0016501546).

BP6

Variant 4-55954246-G-A is Benign according to our data. Variant chr4-55954246-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 128703.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-55954246-G-A is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.027 (4115/152276) while in subpopulation NFE AF= 0.0416 (2832/68012). AF 95% confidence interval is 0.0404. There are 69 homozygotes in gnomad4. There are 1919 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 69 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEP135	NM_025009.5 link	c.335G>A	p.Arg112His	missense_variant	Exon 4 of 26	ENST00000257287.5	NP_079285.2	Q66GS9-1
CEP135	XM_006714055.4 link	c.335G>A	p.Arg112His	missense_variant	Exon 4 of 26		XP_006714118.1
LOC124900705	XR_007058124.1 link	n.198-1775C>T		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CEP135	ENST00000257287.5 link	c.335G>A	p.Arg112His	missense_variant	Exon 4 of 26	1	NM_025009.5	ENSP00000257287.3	Q66GS9-1
CEP135	ENST00000422247.6 link	c.335G>A	p.Arg112His	missense_variant	Exon 4 of 6	2		ENSP00000412799.2	Q66GS9-2
CEP135	ENST00000706800.1 link	n.508G>A		non_coding_transcript_exon_variant	Exon 4 of 5
CEP135	ENST00000515081.1 link	n.-32G>A		upstream_gene_variant		2

Frequencies

GnomAD3 genomes

AF:

0.0271

AC:

4117

AN:

152158

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00830

Gnomad AMI

AF:

0.0208

Gnomad AMR

AF:

0.0255

Gnomad ASJ

AF:

0.0282

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00745

Gnomad FIN

AF:

0.0310

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.0416

Gnomad OTH

AF:

0.0297

GnomAD3 exomes

AF:

0.0285

AC:

6877

AN:

241070

Hom.:

129

AF XY:

0.0294

AC XY:

3838

AN XY:

130456

show subpopulations

Gnomad AFR exome

AF:

0.00696

Gnomad AMR exome

AF:

0.0162

Gnomad ASJ exome

AF:

0.0276

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00964

Gnomad FIN exome

AF:

0.0324

Gnomad NFE exome

AF:

0.0436

Gnomad OTH exome

AF:

0.0321

GnomAD4 exome

AF:

0.0362

AC:

52408

AN:

1447916

Hom.:

1108

Cov.:

AF XY:

0.0357

AC XY:

25695

AN XY:

719994

show subpopulations

Gnomad4 AFR exome

AF:

0.00621

Gnomad4 AMR exome

AF:

0.0169

Gnomad4 ASJ exome

AF:

0.0291

Gnomad4 EAS exome

AF:

0.0000769

Gnomad4 SAS exome

AF:

0.00946

Gnomad4 FIN exome

AF:

0.0324

Gnomad4 NFE exome

AF:

0.0416

Gnomad4 OTH exome

AF:

0.0336

GnomAD4 genome

AF:

0.0270

AC:

4115

AN:

152276

Hom.:

Cov.:

AF XY:

0.0258

AC XY:

1919

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.00828

Gnomad4 AMR

AF:

0.0254

Gnomad4 ASJ

AF:

0.0282

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00745

Gnomad4 FIN

AF:

0.0310

Gnomad4 NFE

AF:

0.0416

Gnomad4 OTH

AF:

0.0289

Alfa

AF:

0.0382

Hom.:

228

Bravo

AF:

0.0261

TwinsUK

AF:

0.0407

AC:

151

ALSPAC

AF:

0.0355

AC:

137

ESP6500AA

AF:

0.00862

AC:

ESP6500EA

AF:

0.0423

AC:

364

ExAC

AF:

0.0284

AC:

3442

Asia WGS

AF:

0.00491

AC:

AN:

3474

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Feb 01, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 14, 2021

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified

Benign:1

Mar 01, 2013

Genetic Services Laboratory, University of Chicago

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.71

BayesDel_noAF

Benign

-0.76

CADD

Benign

DANN

Benign

0.37

DEOGEN2

Benign

0.0043

.;T

Eigen

Benign

-0.99

Eigen_PC

Benign

-0.88

FATHMM_MKL

Benign

0.54

LIST_S2

Benign

0.72

T;T

MetaRNN

Benign

0.0017

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-1.3

N;N

PrimateAI

Benign

0.21

PROVEAN

Benign

1.7

N;N

REVEL

Benign

0.034

Sift

Benign

0.68

T;T

Sift4G

Benign

0.82

T;T

Polyphen

0.0020

B;B

Vest4

0.072

MPC

0.069

ClinPred

0.00056

GERP RS

-0.45

Varity_R

0.097

gMVP

0.15

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