Variant 18-13019082-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_032142.4(CEP192):c.926G>C(p.Ser309Thr) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000509 in 1,375,188 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000051 ( 0 hom. )

Consequence

CEP192
NM_032142.4 missense, splice_region

Scores

Splicing: ADA: 0.001683

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0130

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.058809906).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CEP192	NM_032142.4 linkuse as main transcript	c.926G>C	p.Ser309Thr	missense_variant, splice_region_variant	9/45	ENST00000506447.5	NP_115518.3	Q8TEP8-3Q9HCK3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CEP192	ENST00000506447.5 linkuse as main transcript	c.926G>C	p.Ser309Thr	missense_variant, splice_region_variant	9/45	5	NM_032142.4	ENSP00000427550.1		Q8TEP8-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000151

AC:

AN:

132324

Hom.:

AF XY:

0.0000142

AC XY:

AN XY:

70288

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000572

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000265

GnomAD4 exome

AF:

0.00000509

AC:

AN:

1375188

Hom.:

Cov.:

AF XY:

0.00000590

AC XY:

AN XY:

677992

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000541

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000187

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000434

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000466

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 20, 2024

The c.926G>C (p.S309T) alteration is located in exon 9 (coding exon 8) of the CEP192 gene. This alteration results from a G to C substitution at nucleotide position 926, causing the serine (S) at amino acid position 309 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.099

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.72

CADD

Benign

8.5

DANN

Benign

0.39

DEOGEN2

Benign

0.019

T;.

Eigen

Benign

-0.96

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.061

LIST_S2

Benign

0.33

T;T

M_CAP

Benign

0.011

MetaRNN

Benign

0.059

T;T

MetaSVM

Benign

-0.95

PrimateAI

Benign

0.25

PROVEAN

Benign

-0.63

.;N

REVEL

Benign

0.078

Sift

Benign

0.66

.;T

Sift4G

Pathogenic

0.0

D;T

Vest4

0.041

MutPred

0.13

Gain of glycosylation at S309 (P = 0.045);Gain of glycosylation at S309 (P = 0.045);

MVP

0.21

MPC

0.097

ClinPred

0.071

GERP RS

-0.92

Varity_R

0.046

gMVP

0.092

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0017

dbscSNV1_RF

Benign

0.14

SpliceAI score (max)

0.060

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