Variant 18-13008498-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_032142.4(CEP192):c.333G>C(p.Leu111Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00588 in 1,551,082 control chromosomes in the GnomAD database, including 233 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0088 ( 41 hom., cov: 32)

Exomes 𝑓: 0.0056 ( 192 hom. )

Consequence

CEP192
NM_032142.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.83

Variant links:

Genes affected

CEP192 (HGNC:25515): (centrosomal protein 192) Enables phosphatase binding activity. Involved in centrosome-templated microtubule nucleation; mitotic spindle assembly; and protein localization to centrosome. Located in centriole; centrosome; and cytosol. [provided by Alliance of Genome Resources, Apr 2022]

CEP192 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.002481103).

BP6

Variant 18-13008498-G-C is Benign according to our data. Variant chr18-13008498-G-C is described in ClinVar as [Benign]. Clinvar id is 769934.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr18-13008498-G-C is described in Lovd as [Benign].

BA1

GnomAdExome4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0878 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CEP192	NM_032142.4 linkuse as main transcript	c.333G>C	p.Leu111Phe	missense_variant	4/45	ENST00000506447.5	NP_115518.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CEP192	ENST00000506447.5 linkuse as main transcript	c.333G>C	p.Leu111Phe	missense_variant	4/45	5	NM_032142.4	ENSP00000427550	P1	Q8TEP8-3

Frequencies

GnomAD3 genomes

AF:

0.00873

AC:

1328

AN:

152130

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00263

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0526

Gnomad ASJ

AF:

0.00317

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.0157

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00316

Gnomad OTH

AF:

0.00862

GnomAD3 exomes

AF:

0.0183

AC:

2815

AN:

153516

Hom.:

124

AF XY:

0.0152

AC XY:

1234

AN XY:

81448

show subpopulations

Gnomad AFR exome

AF:

0.00190

Gnomad AMR exome

AF:

0.0924

Gnomad ASJ exome

AF:

0.00177

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00137

Gnomad FIN exome

AF:

0.0180

Gnomad NFE exome

AF:

0.00247

Gnomad OTH exome

AF:

0.0153

GnomAD4 exome

AF:

0.00556

AC:

7780

AN:

1398834

Hom.:

192

Cov.:

AF XY:

0.00525

AC XY:

3621

AN XY:

689914

show subpopulations

Gnomad4 AFR exome

AF:

0.00117

Gnomad4 AMR exome

AF:

0.0904

Gnomad4 ASJ exome

AF:

0.00195

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00124

Gnomad4 FIN exome

AF:

0.0163

Gnomad4 NFE exome

AF:

0.00301

Gnomad4 OTH exome

AF:

0.00538

GnomAD4 genome

AF:

0.00877

AC:

1335

AN:

152248

Hom.:

Cov.:

AF XY:

0.00963

AC XY:

717

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.00262

Gnomad4 AMR

AF:

0.0529

Gnomad4 ASJ

AF:

0.00317

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.000829

Gnomad4 FIN

AF:

0.0157

Gnomad4 NFE

AF:

0.00316

Gnomad4 OTH

AF:

0.00853

Alfa

AF:

0.00361

Hom.:

Bravo

AF:

0.0127

TwinsUK

AF:

0.00405

AC:

ALSPAC

AF:

0.00182

AC:

ExAC

AF:

0.00326

AC:

Asia WGS

AF:

0.00491

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Apr 11, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.084

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.59

CADD

Benign

DANN

Benign

0.93

DEOGEN2

Benign

0.019

T;.

Eigen

Benign

-0.020

Eigen_PC

Benign

-0.11

FATHMM_MKL

Uncertain

0.86

LIST_S2

Benign

0.45

T;T

MetaRNN

Benign

0.0025

T;T

MetaSVM

Benign

-0.98

MutationTaster

Benign

0.99

D;N

PrimateAI

Benign

0.32

PROVEAN

Benign

-0.28

.;N

REVEL

Benign

0.077

Sift

Benign

0.18

.;T

Sift4G

Uncertain

0.042

D;T

Vest4

0.21

MutPred

0.12

Loss of helix (P = 0.1299);Loss of helix (P = 0.1299);

MPC

0.35

ClinPred

0.016

GERP RS

3.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.044

gMVP

0.038

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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