Variant chr18-13017293-C-T 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.746C>T(p.Pro249Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,184 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Consequence

CEP192
NM_032142.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.206

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=0.04294288).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CEP192	NM_032142.4 linkuse as main transcript	c.746C>T	p.Pro249Leu	missense_variant	7/45	ENST00000506447.5	NP_115518.3	Q8TEP8-3Q9HCK3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CEP192	ENST00000506447.5 linkuse as main transcript	c.746C>T	p.Pro249Leu	missense_variant	7/45	5	NM_032142.4	ENSP00000427550.1	Q8TEP8-3
CEP192	ENST00000513432.5 linkuse as main transcript	n.410C>T		non_coding_transcript_exon_variant	4/39	1		ENSP00000424671.1	H0Y9P3
CEP192	ENST00000589596.5 linkuse as main transcript	c.746C>T	p.Pro249Leu	missense_variant	7/18	2		ENSP00000466258.1	K7ELX0
CEP192	ENST00000325971 linkuse as main transcript	c.-470C>T		5_prime_UTR_variant	7/44	5		ENSP00000317156.9	A0A0A0MR42

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152184

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74352

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000113

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

Nov 29, 2024

The c.746C>T (p.P249L) alteration is located in exon 7 (coding exon 6) of the CEP192 gene. This alteration results from a C to T substitution at nucleotide position 746, causing the proline (P) at amino acid position 249 to be replaced by a leucine (L). 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

0.064

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.62

CADD

Benign

1.5

DANN

Benign

0.15

DEOGEN2

Benign

0.0049

T;.

Eigen

Benign

-0.95

Eigen_PC

Benign

-0.93

FATHMM_MKL

Benign

0.016

LIST_S2

Benign

0.67

T;T

M_CAP

Benign

0.013

MetaRNN

Benign

0.043

T;T

MetaSVM

Benign

-0.93

PrimateAI

Benign

0.24

PROVEAN

Benign

0.65

.;N

REVEL

Benign

0.025

Sift

Benign

0.25

.;T

Sift4G

Benign

0.28

T;T

Vest4

0.13

MutPred

0.20

Loss of glycosylation at P249 (P = 0.0228);Loss of glycosylation at P249 (P = 0.0228);

MVP

0.24

MPC

0.099

ClinPred

0.068

GERP RS

1.4

Varity_R

0.039

gMVP

0.040

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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