chr18-13056683-G-A

Position:

• chr18-13056683-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032142.4(CEP192):​c.4093G>A​(p.Val1365Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.136 in 1,601,634 control chromosomes in the GnomAD database, including 16,645 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency:
  • Genomes: 𝑓 0.14 (1589 hom., cov: 33)
  • Exomes 𝑓: 0.14 (15056 hom.)
• Consequence: CEP192 NM_032142.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.561

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0037734509).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.301 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CEP192	NM_032142.4	c.4093G>A	p.Val1365Met	missense_variant	19/45	ENST00000506447.5	NP_115518.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CEP192	ENST00000506447.5	c.4093G>A	p.Val1365Met	missense_variant	19/45	5	NM_032142.4	ENSP00000427550.1

Frequencies

GnomAD3 genomes AF: 0.137 AC: 20878 AN: 152120 Hom.: 1587 Cov.: 33

Gnomad AFR AF: 0.121

Gnomad AMI AF: 0.0866

Gnomad AMR AF: 0.126

Gnomad ASJ AF: 0.192

Gnomad EAS AF: 0.313

Gnomad SAS AF: 0.248

Gnomad FIN AF: 0.119

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.129

Gnomad OTH AF: 0.151

GnomAD3 exomes AF: 0.153 AC: 36168 AN: 236220 Hom.: 3232 AF XY: 0.156 AC XY: 19934 AN XY: 127952

Gnomad AFR exome AF: 0.123

Gnomad AMR exome AF: 0.105

Gnomad ASJ exome AF: 0.196

Gnomad EAS exome AF: 0.316

Gnomad SAS exome AF: 0.234

Gnomad FIN exome AF: 0.122

Gnomad NFE exome AF: 0.127

Gnomad OTH exome AF: 0.150

GnomAD4 exome AF: 0.136 AC: 197403 AN: 1449396 Hom.: 15056 Cov.: 33 AF XY: 0.139 AC XY: 100165 AN XY: 720618

Gnomad4 AFR exome AF: 0.124

Gnomad4 AMR exome AF: 0.104

Gnomad4 ASJ exome AF: 0.190

Gnomad4 EAS exome AF: 0.284

Gnomad4 SAS exome AF: 0.227

Gnomad4 FIN exome AF: 0.124

Gnomad4 NFE exome AF: 0.124

Gnomad4 OTH exome AF: 0.155

GnomAD4 genome AF: 0.137 AC: 20892 AN: 152238 Hom.: 1589 Cov.: 33 AF XY: 0.140 AC XY: 10401 AN XY: 74452

Gnomad4 AFR AF: 0.121

Gnomad4 AMR AF: 0.126

Gnomad4 ASJ AF: 0.192

Gnomad4 EAS AF: 0.313

Gnomad4 SAS AF: 0.248

Gnomad4 FIN AF: 0.119

Gnomad4 NFE AF: 0.129

Gnomad4 OTH AF: 0.154

Alfa AF: 0.136 Hom.: 3712

Bravo AF: 0.135

TwinsUK AF: 0.120 AC: 444

ALSPAC AF: 0.119 AC: 459

ESP6500AA AF: 0.119 AC: 524

ESP6500EA AF: 0.127 AC: 1096

ExAC AF: 0.151 AC: 18303

Asia WGS AF: 0.265 AC: 921 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.068
BayesDel_addAF	Benign	-0.83	T
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.25
DANN	Benign	0.073
DEOGEN2	Benign	0.0028	T;T;T
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.0066	N
LIST_S2	Benign	0.073	T;T;T
MetaRNN	Benign	0.0038	T;T;T
MetaSVM	Benign	-0.97	T
PrimateAI	Benign	0.25	T
PROVEAN	Benign	0.49	.;N;.
REVEL	Benign	0.0080
Sift	Benign	1.0	.;T;.
Sift4G	Benign	0.59	T;T;T
Vest4		0.031, 0.012
MPC		0.097
ClinPred		0.00026	T
GERP RS		-2.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.017
gMVP		0.16

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

LitVar

Other links and lift over

dbSNP: rs2282542; hg19: chr18-13056682; COSMIC: COSV58059891; COSMIC: COSV58059891;