Variant 11-93679421-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_033395.2(CEP295):c.634C>T(p.Arg212Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00157 in 1,548,786 control chromosomes in the GnomAD database, including 42 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0083 ( 23 hom., cov: 32)

Exomes 𝑓: 0.00084 ( 19 hom. )

Consequence

CEP295
NM_033395.2 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 5.25

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0032111704).

BP6

Variant 11-93679421-C-T is Benign according to our data. Variant chr11-93679421-C-T is described in ClinVar as [Benign]. Clinvar id is 776647.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00828 (1261/152208) while in subpopulation AFR AF= 0.0288 (1196/41518). AF 95% confidence interval is 0.0274. There are 23 homozygotes in gnomad4. There are 577 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 23 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CEP295	NM_033395.2 linkuse as main transcript	c.634C>T	p.Arg212Cys	missense_variant	7/30	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.634C>T	p.Arg212Cys	missense_variant	7/30	2	NM_033395.2	ENSP00000316681.6		Q9C0D2-1

Frequencies

GnomAD3 genomes

AF:

0.00830

AC:

1262

AN:

152090

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0289

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00288

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.00573

GnomAD3 exomes

AF:

0.00189

AC:

294

AN:

155586

Hom.:

AF XY:

0.00136

AC XY:

112

AN XY:

82262

show subpopulations

Gnomad AFR exome

AF:

0.0315

Gnomad AMR exome

AF:

0.00144

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000166

Gnomad OTH exome

AF:

0.00160

GnomAD4 exome

AF:

0.000841

AC:

1175

AN:

1396578

Hom.:

Cov.:

AF XY:

0.000739

AC XY:

509

AN XY:

688756

show subpopulations

Gnomad4 AFR exome

AF:

0.0313

Gnomad4 AMR exome

AF:

0.00155

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000635

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000149

Gnomad4 OTH exome

AF:

0.00195

GnomAD4 genome

AF:

0.00828

AC:

1261

AN:

152208

Hom.:

Cov.:

AF XY:

0.00775

AC XY:

577

AN XY:

74434

show subpopulations

Gnomad4 AFR

AF:

0.0288

Gnomad4 AMR

AF:

0.00288

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.00567

Alfa

AF:

0.00147

Hom.:

Bravo

AF:

0.00987

ESP6500AA

AF:

0.0238

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00293

AC:

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.44

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.040

Eigen

Uncertain

0.44

Eigen_PC

Uncertain

0.52

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.92

MetaRNN

Benign

0.0032

MetaSVM

Benign

-1.1

PrimateAI

Benign

0.23

PROVEAN

Uncertain

-2.8

REVEL

Benign

0.12

Sift

Uncertain

0.023

Sift4G

Uncertain

0.0080

Polyphen

0.99

Vest4

0.14

MVP

0.15

MPC

0.32

ClinPred

0.075

GERP RS

5.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.13

gMVP

0.16

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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