4-55953268-C-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_025009.5(CEP135):c.297C>T(p.His99His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000865 in 1,508,172 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0029 ( 1 hom., cov: 33)

Exomes 𝑓: 0.00063 ( 4 hom. )

Consequence

CEP135
NM_025009.5 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -1.23

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 4-55953268-C-T is Benign according to our data. Variant chr4-55953268-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 128700.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-55953268-C-T is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=-1.23 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00294 (448/152170) while in subpopulation AFR AF= 0.00913 (379/41532). AF 95% confidence interval is 0.00837. There are 1 homozygotes in gnomad4. There are 213 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEP135	NM_025009.5 link	c.297C>T	p.His99His	synonymous_variant	Exon 3 of 26	ENST00000257287.5	NP_079285.2	Q66GS9-1
CEP135	XM_006714055.4 link	c.297C>T	p.His99His	synonymous_variant	Exon 3 of 26		XP_006714118.1
LOC124900705	XR_007058124.1 link	n.198-797G>A		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CEP135	ENST00000257287.5 link	c.297C>T	p.His99His	synonymous_variant	Exon 3 of 26	1	NM_025009.5	ENSP00000257287.3	Q66GS9-1
CEP135	ENST00000422247.6 link	c.297C>T	p.His99His	synonymous_variant	Exon 3 of 6	2		ENSP00000412799.2	Q66GS9-2
CEP135	ENST00000706800.1 link	n.470C>T		non_coding_transcript_exon_variant	Exon 3 of 5

Frequencies

GnomAD3 genomes

AF:

0.00295

AC:

448

AN:

152052

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00915

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00138

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00318

Gnomad NFE

AF:

0.000485

Gnomad OTH

AF:

0.00574

GnomAD3 exomes

AF:

0.00115

AC:

207

AN:

180528

Hom.:

AF XY:

0.000946

AC XY:

AN XY:

99418

show subpopulations

Gnomad AFR exome

AF:

0.00971

Gnomad AMR exome

AF:

0.00203

Gnomad ASJ exome

AF:

0.000168

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000397

Gnomad OTH exome

AF:

0.00337

GnomAD4 exome

AF:

0.000631

AC:

856

AN:

1356002

Hom.:

Cov.:

AF XY:

0.000608

AC XY:

407

AN XY:

668926

show subpopulations

Gnomad4 AFR exome

AF:

0.0110

Gnomad4 AMR exome

AF:

0.00193

Gnomad4 ASJ exome

AF:

0.000410

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000418

Gnomad4 FIN exome

AF:

0.0000197

Gnomad4 NFE exome

AF:

0.000361

Gnomad4 OTH exome

AF:

0.00139

GnomAD4 genome

AF:

0.00294

AC:

448

AN:

152170

Hom.:

Cov.:

AF XY:

0.00286

AC XY:

213

AN XY:

74396

show subpopulations

Gnomad4 AFR

AF:

0.00913

Gnomad4 AMR

AF:

0.00137

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000485

Gnomad4 OTH

AF:

0.00568

Alfa

AF:

0.00144

Hom.:

Bravo

AF:

0.00369

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Jun 25, 2020

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

- -

Jan 05, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Sep 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

CEP135: BP4, BP7 -

not specified

Benign:1

Dec 03, 2013

Genetic Services Laboratory, University of Chicago

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

CEP135-related disorder

Benign:1

Jun 07, 2021

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

0.62

DANN

Benign

0.37

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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