Variant rs78544176 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_033395.2(CEP295):c.6309C>G(p.Asp2103Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.06 in 1,546,140 control chromosomes in the GnomAD database, including 3,300 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.046 ( 242 hom., cov: 33)

Exomes 𝑓: 0.062 ( 3058 hom. )

Consequence

CEP295
NM_033395.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0950

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 -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0021867156).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0725 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CEP295	NM_033395.2 linkuse as main transcript	c.6309C>G	p.Asp2103Glu	missense_variant	22/30	ENST00000325212.11	NP_203753.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CEP295	ENST00000325212.11 linkuse as main transcript	c.6309C>G	p.Asp2103Glu	missense_variant	22/30	2	NM_033395.2	ENSP00000316681	A2	Q9C0D2-1
CEP295	ENST00000531700.5 linkuse as main transcript	c.849C>G	p.Asp283Glu	missense_variant	9/17	2		ENSP00000437323	P4	Q9C0D2-2
CEP295	ENST00000531404.1 linkuse as main transcript	c.345C>G	p.Asp115Glu	missense_variant	2/9	2		ENSP00000433650
CEP295	ENST00000529185.1 linkuse as main transcript	c.-94C>G		5_prime_UTR_variant	1/3	3		ENSP00000433198

Frequencies

GnomAD3 genomes

AF:

0.0464

AC:

7054

AN:

152156

Hom.:

242

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0126

Gnomad AMI

AF:

0.105

Gnomad AMR

AF:

0.0374

Gnomad ASJ

AF:

0.0179

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.00870

Gnomad FIN

AF:

0.0586

Gnomad MID

AF:

0.0255

Gnomad NFE

AF:

0.0742

Gnomad OTH

AF:

0.0411

GnomAD3 exomes

AF:

0.0417

AC:

6488

AN:

155546

Hom.:

183

AF XY:

0.0406

AC XY:

3348

AN XY:

82396

show subpopulations

Gnomad AFR exome

AF:

0.0106

Gnomad AMR exome

AF:

0.0250

Gnomad ASJ exome

AF:

0.0226

Gnomad EAS exome

AF:

0.0000919

Gnomad SAS exome

AF:

0.0136

Gnomad FIN exome

AF:

0.0571

Gnomad NFE exome

AF:

0.0688

Gnomad OTH exome

AF:

0.0445

GnomAD4 exome

AF:

0.0615

AC:

85733

AN:

1393866

Hom.:

3058

Cov.:

AF XY:

0.0605

AC XY:

41571

AN XY:

687678

show subpopulations

Gnomad4 AFR exome

AF:

0.00888

Gnomad4 AMR exome

AF:

0.0265

Gnomad4 ASJ exome

AF:

0.0219

Gnomad4 EAS exome

AF:

0.0000560

Gnomad4 SAS exome

AF:

0.0133

Gnomad4 FIN exome

AF:

0.0598

Gnomad4 NFE exome

AF:

0.0715

Gnomad4 OTH exome

AF:

0.0529

GnomAD4 genome

AF:

0.0463

AC:

7054

AN:

152274

Hom.:

242

Cov.:

AF XY:

0.0452

AC XY:

3369

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.0125

Gnomad4 AMR

AF:

0.0372

Gnomad4 ASJ

AF:

0.0179

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.00892

Gnomad4 FIN

AF:

0.0586

Gnomad4 NFE

AF:

0.0742

Gnomad4 OTH

AF:

0.0407

Alfa

AF:

0.0629

Hom.:

256

Bravo

AF:

0.0437

TwinsUK

AF:

0.0761

AC:

282

ALSPAC

AF:

0.0791

AC:

305

ESP6500AA

AF:

0.0166

AC:

ESP6500EA

AF:

0.0685

AC:

218

ExAC

AF:

0.0325

AC:

780

Asia WGS

AF:

0.00693

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.32

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.58

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.020

T;.;T

Eigen

Uncertain

0.21

Eigen_PC

Uncertain

0.25

FATHMM_MKL

Uncertain

0.78

LIST_S2

Benign

0.74

T;T;T

MetaRNN

Benign

0.0022

T;T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

0.96

N;N;N;N

PrimateAI

Benign

0.35

PROVEAN

Benign

-1.6

N;N;D

REVEL

Benign

0.060

Sift

Benign

0.12

T;T;T

Sift4G

Benign

0.34

T;T;T

Polyphen

0.87

P;P;.

Vest4

0.16

MutPred

0.16

Gain of helix (P = 0.0854);.;.;

MPC

0.31

ClinPred

0.019

GERP RS

3.5

Varity_R

0.099

gMVP

0.035

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over