Variant 18-13018559-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_032142.4(CEP192):c.869C>T(p.Ser290Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000072 in 1,389,838 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.2e-7 ( 0 hom. )

Consequence

CEP192
NM_032142.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.891

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 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=0.1742911).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CEP192	NM_032142.4 linkuse as main transcript	c.869C>T	p.Ser290Phe	missense_variant	8/45	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.869C>T	p.Ser290Phe	missense_variant	8/45	5	NM_032142.4	ENSP00000427550	P1	Q8TEP8-3
CEP192	ENST00000513432.5 linkuse as main transcript	c.536C>T	p.Ser179Phe	missense_variant, NMD_transcript_variant	5/39	1		ENSP00000424671
CEP192	ENST00000589596.5 linkuse as main transcript	c.869C>T	p.Ser290Phe	missense_variant	8/18	2		ENSP00000466258
CEP192	ENST00000325971.12 linkuse as main transcript	c.-347C>T		5_prime_UTR_variant	8/44	5		ENSP00000317156

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.20e-7

AC:

AN:

1389838

Hom.:

Cov.:

AF XY:

0.00000146

AC XY:

AN XY:

685752

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000174

GnomAD4 genome

Cov.:

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

Jun 18, 2021

The c.869C>T (p.S290F) alteration is located in exon 8 (coding exon 7) of the CEP192 gene. This alteration results from a C to T substitution at nucleotide position 869, causing the serine (S) at amino acid position 290 to be replaced by a phenylalanine (F). 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

0.16

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0028

T;.

Eigen

Benign

-0.13

Eigen_PC

Benign

-0.25

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.60

T;T

M_CAP

Benign

0.028

MetaRNN

Benign

0.17

T;T

MetaSVM

Benign

-1.1

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.30

PROVEAN

Benign

-1.4

.;N

REVEL

Benign

0.045

Sift

Uncertain

0.0050

.;D

Sift4G

Uncertain

0.0090

D;T

Vest4

0.28

MutPred

0.22

Loss of phosphorylation at S290 (P = 0.0089);Loss of phosphorylation at S290 (P = 0.0089);

MVP

0.44

MPC

0.51

ClinPred

0.80

GERP RS

2.9

Varity_R

0.093

gMVP

0.17

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over