Variant 11-93675577-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_033395.2(CEP295):c.535G>A(p.Glu179Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0125 in 1,470,798 control chromosomes in the GnomAD database, including 175 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0091 ( 11 hom., cov: 33)

Exomes 𝑓: 0.013 ( 164 hom. )

Consequence

CEP295
NM_033395.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 2.98

Variant links:

Genes affected

CEP295 (HGNC:29366): (centrosomal protein 295) Enables microtubule binding activity. Involved in several processes, including centriole replication; positive regulation of protein acetylation; and regulation of centrosome duplication. Located in cytosol; microtubule cytoskeleton; and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

CEP295 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0017814636).

BP6

Variant 11-93675577-G-A is Benign according to our data. Variant chr11-93675577-G-A is described in ClinVar as [Benign]. Clinvar id is 777857.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 11 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CEP295	NM_033395.2 linkuse as main transcript	c.535G>A	p.Glu179Lys	missense_variant	6/30	ENST00000325212.11	NP_203753.1	Q9C0D2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CEP295	ENST00000325212.11 linkuse as main transcript	c.535G>A	p.Glu179Lys	missense_variant	6/30	2	NM_033395.2	ENSP00000316681.6		Q9C0D2-1

Frequencies

GnomAD3 genomes

AF:

0.00916

AC:

1391

AN:

151858

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00280

Gnomad AMI

AF:

0.00220

Gnomad AMR

AF:

0.00879

Gnomad ASJ

AF:

0.0372

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.00569

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0136

Gnomad OTH

AF:

0.0106

GnomAD3 exomes

AF:

0.0106

AC:

1159

AN:

108874

Hom.:

AF XY:

0.00990

AC XY:

583

AN XY:

58894

show subpopulations

Gnomad AFR exome

AF:

0.00180

Gnomad AMR exome

AF:

0.00867

Gnomad ASJ exome

AF:

0.0371

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00181

Gnomad FIN exome

AF:

0.00561

Gnomad NFE exome

AF:

0.0137

Gnomad OTH exome

AF:

0.0134

GnomAD4 exome

AF:

0.0129

AC:

17061

AN:

1318822

Hom.:

164

Cov.:

AF XY:

0.0126

AC XY:

8232

AN XY:

651586

show subpopulations

Gnomad4 AFR exome

AF:

0.00171

Gnomad4 AMR exome

AF:

0.00977

Gnomad4 ASJ exome

AF:

0.0373

Gnomad4 EAS exome

AF:

0.0000315

Gnomad4 SAS exome

AF:

0.00211

Gnomad4 FIN exome

AF:

0.00661

Gnomad4 NFE exome

AF:

0.0142

Gnomad4 OTH exome

AF:

0.0131

GnomAD4 genome

AF:

0.00914

AC:

1389

AN:

151976

Hom.:

Cov.:

AF XY:

0.00835

AC XY:

620

AN XY:

74272

show subpopulations

Gnomad4 AFR

AF:

0.00280

Gnomad4 AMR

AF:

0.00878

Gnomad4 ASJ

AF:

0.0372

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00125

Gnomad4 FIN

AF:

0.00569

Gnomad4 NFE

AF:

0.0135

Gnomad4 OTH

AF:

0.0104

Alfa

AF:

0.0137

Hom.:

Bravo

AF:

0.00995

TwinsUK

AF:

0.0105

AC:

ALSPAC

AF:

0.0117

AC:

ESP6500AA

AF:

0.00217

AC:

ESP6500EA

AF:

0.0179

AC:

ExAC

AF:

0.00950

AC:

219

Asia WGS

AF:

0.00145

AC:

AN:

3474

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Oct 01, 2024	CEP295: BP4, BS1, BS2 -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 11, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.23

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.57

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.021

Eigen

Benign

-0.48

Eigen_PC

Benign

-0.25

FATHMM_MKL

Uncertain

0.86

LIST_S2

Benign

0.78

MetaRNN

Benign

0.0018

MetaSVM

Benign

-0.94

PrimateAI

Benign

0.35

PROVEAN

Benign

-1.8

REVEL

Benign

0.051

Sift

Benign

0.27

Sift4G

Benign

0.21

Polyphen

0.022

Vest4

0.16

MPC

0.15

ClinPred

0.013

GERP RS

3.8

Varity_R

0.19

gMVP

0.23

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