18-13008498-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_032142.4(CEP192):c.333G>C(p.Leu111Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00588 in 1,551,082 control chromosomes in the GnomAD database, including 233 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0088 (41 hom., cov: 32)
  • Exomes 𝑓: 0.0056 (192 hom.)
• Consequence: CEP192 NM_032142.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.83

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.002481103).
• BP6: Variant 18-13008498-G-C is Benign according to our data. Variant chr18-13008498-G-C is described in ClinVar as [Benign]. Clinvar id is 769934.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr18-13008498-G-C is described in Lovd as [Benign].
• BA1: GnomAdExome4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0878 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CEP192	NM_032142.4	c.333G>C	p.Leu111Phe	missense_variant	4/45	ENST00000506447.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CEP192	ENST00000506447.5	c.333G>C	p.Leu111Phe	missense_variant	4/45	5	NM_032142.4	P1

Frequencies

GnomAD3 genomes AF: 0.00873 AC: 1328 AN: 152130 Hom.: 42 Cov.: 32

Gnomad AFR AF: 0.00263

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0526

Gnomad ASJ AF: 0.00317

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.0157

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00316

Gnomad OTH AF: 0.00862

GnomAD3 exomes AF: 0.0183 AC: 2815 AN: 153516 Hom.: 124 AF XY: 0.0152 AC XY: 1234 AN XY: 81448

Gnomad AFR exome AF: 0.00190

Gnomad AMR exome AF: 0.0924

Gnomad ASJ exome AF: 0.00177

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00137

Gnomad FIN exome AF: 0.0180

Gnomad NFE exome AF: 0.00247

Gnomad OTH exome AF: 0.0153

GnomAD4 exome AF: 0.00556 AC: 7780 AN: 1398834 Hom.: 192 Cov.: 31 AF XY: 0.00525 AC XY: 3621 AN XY: 689914

Gnomad4 AFR exome AF: 0.00117

Gnomad4 AMR exome AF: 0.0904

Gnomad4 ASJ exome AF: 0.00195

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00124

Gnomad4 FIN exome AF: 0.0163

Gnomad4 NFE exome AF: 0.00301

Gnomad4 OTH exome AF: 0.00538

GnomAD4 genome AF: 0.00877 AC: 1335 AN: 152248 Hom.: 41 Cov.: 32 AF XY: 0.00963 AC XY: 717 AN XY: 74442

Gnomad4 AFR AF: 0.00262

Gnomad4 AMR AF: 0.0529

Gnomad4 ASJ AF: 0.00317

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.000829

Gnomad4 FIN AF: 0.0157

Gnomad4 NFE AF: 0.00316

Gnomad4 OTH AF: 0.00853

Alfa AF: 0.00361 Hom.: 5

Bravo AF: 0.0127

TwinsUK AF: 0.00405 AC: 15

ALSPAC AF: 0.00182 AC: 7

ExAC AF: 0.00326 AC: 75

Asia WGS AF: 0.00491 AC: 17 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Apr 11, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.62	T
BayesDel_noAF	Benign	-0.59
Cadd	Benign	17
Dann	Benign	0.93
DEOGEN2	Benign	0.019	T;.
Eigen	Benign	-0.020
Eigen_PC	Benign	-0.11
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.45	T;T
MetaRNN	Benign	0.0025	T;T
MetaSVM	Benign	-0.98	T
MutationTaster	Benign	0.99	D;N
PrimateAI	Benign	0.32	T
Sift4G	Uncertain	0.042	D;T
Vest4		0.21
MutPred		0.12		Loss of helix (P = 0.1299);Loss of helix (P = 0.1299);
MPC		0.35
ClinPred		0.016	T
GERP RS		3.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.044
gMVP		0.038

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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

Other links and lift over

dbSNP: rs149216711; hg19: chr18-13008497; COSMIC: COSV100382561; COSMIC: COSV100382561;