Genetic Variant CEP295:p.Glu179Lys (chr11-93675577-G-A) – ACMG Classification: Benign (-16 pts)

Variant summary

Our verdict is Benign. The variant received -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. 12/20 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

Publications

5 publications found

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 was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
CEP295	NM_033395.2 link	c.535G>A	p.Glu179Lys	missense_variant	Exon 6 of 30	ENST00000325212.11	NP_203753.1	Q9C0D2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CEP295	ENST00000325212.11 link	c.535G>A	p.Glu179Lys	missense_variant	Exon 6 of 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

GnomAD2 exomes

AF:

0.0106

AC:

1159

AN:

108874

AF XY:

0.00990

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 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

African (AFR)

AF:

0.00171

AC:

AN:

27448

American (AMR)

AF:

0.00977

AC:

210

AN:

21502

Ashkenazi Jewish (ASJ)

AF:

0.0373

AC:

879

AN:

23568

East Asian (EAS)

AF:

0.0000315

AC:

AN:

31796

South Asian (SAS)

AF:

0.00211

AC:

145

AN:

68582

European-Finnish (FIN)

AF:

0.00661

AC:

322

AN:

48692

Middle Eastern (MID)

AF:

0.00163

AC:

AN:

5520

European-Non Finnish (NFE)

AF:

0.0142

AC:

14727

AN:

1036870

Other (OTH)

AF:

0.0131

AC:

721

AN:

54844

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.461

Heterozygous variant carriers

646

1293

1939

2586

3232

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00914

AC:

1389

AN:

151976

Hom.:

Cov.:

AF XY:

0.00835

AC XY:

620

AN XY:

74272

show subpopulations

African (AFR)

AF:

0.00280

AC:

116

AN:

41480

American (AMR)

AF:

0.00878

AC:

134

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.0372

AC:

129

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.00125

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00569

AC:

AN:

10548

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0135

AC:

920

AN:

67900

Other (OTH)

AF:

0.0104

AC:

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

155

232

310

387

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0132

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

Oct 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

CEP295: BP4, BS1, BS2 -

Jan 11, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

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

(source)

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

PhyloP100

3.0

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

Mutation Taster

=293/7

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

11-93675577-G-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over