rs76941356

Positions:

Variant summary

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

The NM_025009.5(CEP135):c.636A>C(p.Glu212Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000885 in 1,614,140 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0015 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00082 ( 7 hom. )

Consequence

CEP135
NM_025009.5 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.25

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=0.00460732).

BP6

Variant 4-55959703-A-C is Benign according to our data. Variant chr4-55959703-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 210683.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-55959703-A-C is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00154 (234/152362) while in subpopulation EAS AF= 0.00366 (19/5186). AF 95% confidence interval is 0.0024. There are 1 homozygotes in gnomad4. There are 178 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
CEP135	NM_025009.5 linkuse as main transcript	c.636A>C	p.Glu212Asp	missense_variant	6/26	ENST00000257287.5
LOC124900705	XR_007058124.1 linkuse as main transcript	n.198-7232T>G		intron_variant, non_coding_transcript_variant
CEP135	XM_006714055.4 linkuse as main transcript	c.636A>C	p.Glu212Asp	missense_variant	6/26

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CEP135	ENST00000257287.5 linkuse as main transcript	c.636A>C	p.Glu212Asp	missense_variant	6/26	1	NM_025009.5	P1	Q66GS9-1
CEP135	ENST00000422247.6 linkuse as main transcript	c.636A>C	p.Glu212Asp	missense_variant	6/6	2			Q66GS9-2
CEP135	ENST00000515081.1 linkuse as main transcript	n.270A>C		non_coding_transcript_exon_variant	3/5	2
CEP135	ENST00000706800.1 linkuse as main transcript	n.3126A>C		non_coding_transcript_exon_variant	5/5

Frequencies

GnomAD3 genomes

AF:

0.00154

AC:

234

AN:

152244

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00366

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.0182

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000220

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00181

AC:

455

AN:

251362

Hom.:

AF XY:

0.00183

AC XY:

248

AN XY:

135852

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00223

Gnomad SAS exome

AF:

0.000294

Gnomad FIN exome

AF:

0.0147

Gnomad NFE exome

AF:

0.000625

Gnomad OTH exome

AF:

0.00244

GnomAD4 exome

AF:

0.000817

AC:

1195

AN:

1461778

Hom.:

Cov.:

AF XY:

0.000809

AC XY:

588

AN XY:

727186

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00423

Gnomad4 SAS exome

AF:

0.000626

Gnomad4 FIN exome

AF:

0.0145

Gnomad4 NFE exome

AF:

0.000110

Gnomad4 OTH exome

AF:

0.00128

GnomAD4 genome

AF:

0.00154

AC:

234

AN:

152362

Hom.:

Cov.:

AF XY:

0.00239

AC XY:

178

AN XY:

74506

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00366

Gnomad4 SAS

AF:

0.00145

Gnomad4 FIN

AF:

0.0182

Gnomad4 NFE

AF:

0.000220

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000370

Hom.:

Bravo

AF:

0.000257

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.00183

AC:

222

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Dec 11, 2019

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Nov 27, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.35

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.024

.;T

Eigen

Benign

0.18

Eigen_PC

Benign

0.17

FATHMM_MKL

Uncertain

0.76

LIST_S2

Benign

0.80

T;T

MetaRNN

Benign

0.0046

T;T

MetaSVM

Benign

-0.63

MutationAssessor

Benign

1.7

L;L

MutationTaster

Benign

0.96

D;D

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-2.0

N;N

REVEL

Benign

0.17

Sift

Benign

0.12

T;T

Sift4G

Benign

0.25

T;T

Polyphen

1.0

D;B

Vest4

0.11

MutPred

0.099

Loss of disorder (P = 0.2511);Loss of disorder (P = 0.2511);

MVP

0.65

MPC

0.25

ClinPred

0.041

GERP RS

3.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.17

gMVP

0.64

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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