rs376452872

Positions:

chr15-48781208-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001194998.2(CEP152):c.1565C>G(p.Ser522Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000707 in 1,613,254 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.00034 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000043 ( 0 hom. )

Consequence

CEP152
NM_001194998.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:3

Conservation

PhyloP100: 6.00

Variant links:

Genes affected

CEP152 (HGNC:29298): (centrosomal protein 152) This gene encodes a protein that is thought to be involved with centrosome function. Mutations in this gene have been associated with primary microcephaly (MCPH4). Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2010]

CEP152 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.14733776).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CEP152	NM_001194998.2 linkuse as main transcript	c.1565C>G	p.Ser522Cys	missense_variant	12/27	ENST00000380950.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CEP152	ENST00000380950.7 linkuse as main transcript	c.1565C>G	p.Ser522Cys	missense_variant	12/27	1	NM_001194998.2	A2	O94986-4
CEP152	ENST00000399334.7 linkuse as main transcript	c.1565C>G	p.Ser522Cys	missense_variant	12/26	1		P2	O94986-3
CEP152	ENST00000325747.9 linkuse as main transcript	c.1286C>G	p.Ser429Cys	missense_variant	11/25	1		A2	O94986-1
CEP152	ENST00000560322.5 linkuse as main transcript	c.1565C>G	p.Ser522Cys	missense_variant	12/13	1

Frequencies

GnomAD3 genomes

AF:

0.000322

AC:

AN:

152078

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00111

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000843

AC:

AN:

249200

Hom.:

AF XY:

0.0000370

AC XY:

AN XY:

135236

show subpopulations

Gnomad AFR exome

AF:

0.00110

Gnomad AMR exome

AF:

0.000116

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000431

AC:

AN:

1461058

Hom.:

Cov.:

AF XY:

0.0000330

AC XY:

AN XY:

726878

show subpopulations

Gnomad4 AFR exome

AF:

0.00135

Gnomad4 AMR exome

AF:

0.000134

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.000116

GnomAD4 genome

AF:

0.000335

AC:

AN:

152196

Hom.:

Cov.:

AF XY:

0.000282

AC XY:

AN XY:

74414

show subpopulations

Gnomad4 AFR

AF:

0.00116

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000141

Hom.:

Bravo

AF:

0.000374

ESP6500AA

AF:

0.000277

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000828

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Uncertain:2

Uncertain significance, criteria provided, single submitter	clinical testing	Invitae	Jul 02, 2022	This sequence change replaces serine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 522 of the CEP152 protein (p.Ser522Cys). This variant is present in population databases (rs376452872, gnomAD 0.1%). This variant has not been reported in the literature in individuals affected with CEP152-related conditions. ClinVar contains an entry for this variant (Variation ID: 158228). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -
Uncertain significance, criteria provided, single submitter	clinical testing	GeneDx	Mar 20, 2023	In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -

Microcephaly 9, primary, autosomal recessive

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Jan 10, 2013

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.17

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.11

T;.;.

Eigen

Uncertain

0.68

Eigen_PC

Uncertain

0.62

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.81

T;T;T

M_CAP

Benign

0.017

MetaRNN

Benign

0.15

T;T;T

MetaSVM

Uncertain

0.17

MutationAssessor

Uncertain

2.6

M;M;.

MutationTaster

Benign

0.63

N;N;N

PrimateAI

Benign

0.37

PROVEAN

Uncertain

-3.0

D;D;D

REVEL

Uncertain

0.35

Sift

Benign

0.036

D;D;T

Sift4G

Uncertain

0.018

D;D;D

Polyphen

1.0

D;.;D

Vest4

0.48

MVP

0.96

MPC

0.34

ClinPred

0.26

GERP RS

6.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.20

gMVP

0.18

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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