Variant chr18-12999534-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_032142.4(CEP192):c.110G>T(p.Gly37Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000145 in 1,550,888 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.00016 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00014 ( 0 hom. )

Consequence

CEP192
NM_032142.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 7.45

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CEP192	NM_032142.4 linkuse as main transcript	c.110G>T	p.Gly37Val	missense_variant	2/45	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.110G>T	p.Gly37Val	missense_variant	2/45	5	NM_032142.4	ENSP00000427550.1	Q8TEP8-3
CEP192	ENST00000589596.5 linkuse as main transcript	c.110G>T	p.Gly37Val	missense_variant	2/18	2		ENSP00000466258.1	K7ELX0
CEP192	ENST00000325971 linkuse as main transcript	c.-1106G>T		5_prime_UTR_variant	2/44	5		ENSP00000317156.9	A0A0A0MR42
CEP192	ENST00000507064.2 linkuse as main transcript	n.110G>T		non_coding_transcript_exon_variant	2/5	3		ENSP00000476907.1	V9GYM2

Frequencies

GnomAD3 genomes

AF:

0.000164

AC:

AN:

152120

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.000338

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000111

AC:

AN:

153374

Hom.:

AF XY:

0.000111

AC XY:

AN XY:

81444

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000118

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000269

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000143

AC:

200

AN:

1398650

Hom.:

Cov.:

AF XY:

0.000139

AC XY:

AN XY:

689878

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000564

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000126

Gnomad4 FIN exome

AF:

0.0000203

Gnomad4 NFE exome

AF:

0.000176

Gnomad4 OTH exome

AF:

0.0000690

GnomAD4 genome

AF:

0.000164

AC:

AN:

152238

Hom.:

Cov.:

AF XY:

0.000107

AC XY:

AN XY:

74434

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000338

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000241

Hom.:

Bravo

AF:

0.000159

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000314

AC:

ExAC

AF:

0.0000455

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 13, 2022

The c.110G>T (p.G37V) alteration is located in exon 2 (coding exon 1) of the CEP192 gene. This alteration results from a G to T substitution at nucleotide position 110, causing the glycine (G) at amino acid position 37 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.56

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.13

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.19

T;.

Eigen

Uncertain

0.65

Eigen_PC

Pathogenic

0.67

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.82

T;T

M_CAP

Uncertain

0.23

MetaRNN

Uncertain

0.66

D;D

MetaSVM

Benign

-0.65

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.52

PROVEAN

Uncertain

-3.9

.;D

REVEL

Uncertain

0.47

Sift

Pathogenic

0.0

.;D

Sift4G

Pathogenic

0.0

D;D

Vest4

0.83

MVP

0.71

MPC

0.56

ClinPred

0.79

GERP RS

5.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.66

gMVP

0.45

Splicing

Name

Calibrated prediction

Score

Prediction

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