18-13015390-C-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_032142.4(CEP192):c.582C>G(p.His194Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00689 in 1,549,756 control chromosomes in the GnomAD database, including 46 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0049 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0071 (45 hom.)
• Consequence: CEP192 NM_032142.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0490

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0029313564).
• BP6: Variant 18-13015390-C-G is Benign according to our data. Variant chr18-13015390-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 2648604.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CEP192	NM_032142.4	c.582C>G	p.His194Gln	missense_variant	6/45	ENST00000506447.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CEP192	ENST00000506447.5	c.582C>G	p.His194Gln	missense_variant	6/45	5	NM_032142.4	P1
CEP192	ENST00000513432.5	c.249C>G	p.His83Gln	missense_variant, NMD_transcript_variant	3/39	1
CEP192	ENST00000589596.5	c.582C>G	p.His194Gln	missense_variant	6/18	2
CEP192	ENST00000325971.12	c.-634C>G		5_prime_UTR_variant	6/44	5

Frequencies

GnomAD3 genomes AF: 0.00489 AC: 744 AN: 152220 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00125

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00124

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00310

Gnomad FIN AF: 0.00904

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00811

Gnomad OTH AF: 0.00382

GnomAD3 exomes AF: 0.00508 AC: 781 AN: 153844 Hom.: 2 AF XY: 0.00508 AC XY: 415 AN XY: 81620

Gnomad AFR exome AF: 0.00164

Gnomad AMR exome AF: 0.000974

Gnomad ASJ exome AF: 0.000118

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00286

Gnomad FIN exome AF: 0.00977

Gnomad NFE exome AF: 0.00849

Gnomad OTH exome AF: 0.00533

GnomAD4 exome AF: 0.00711 AC: 9935 AN: 1397418 Hom.: 45 Cov.: 30 AF XY: 0.00697 AC XY: 4806 AN XY: 689296

Gnomad4 AFR exome AF: 0.000983

Gnomad4 AMR exome AF: 0.000925

Gnomad4 ASJ exome AF: 0.0000795

Gnomad4 EAS exome AF: 0.0000280

Gnomad4 SAS exome AF: 0.00309

Gnomad4 FIN exome AF: 0.00983

Gnomad4 NFE exome AF: 0.00822

Gnomad4 OTH exome AF: 0.00470

GnomAD4 genome AF: 0.00488 AC: 744 AN: 152338 Hom.: 1 Cov.: 32 AF XY: 0.00443 AC XY: 330 AN XY: 74502

Gnomad4 AFR AF: 0.00125

Gnomad4 AMR AF: 0.00124

Gnomad4 ASJ AF: 0.000576

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00311

Gnomad4 FIN AF: 0.00904

Gnomad4 NFE AF: 0.00811

Gnomad4 OTH AF: 0.00378

Alfa AF: 0.00678 Hom.: 3

Bravo AF: 0.00413

TwinsUK AF: 0.00701 AC: 26

ALSPAC AF: 0.00701 AC: 27

ESP6500AA AF: 0.000723 AC: 1

ESP6500EA AF: 0.00880 AC: 28

ExAC AF: 0.00400 AC: 90

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Sep 01, 2022

CEP192: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.64	T
BayesDel_noAF	Benign	-0.68
Cadd	Benign	1.1
Dann	Benign	0.94
DEOGEN2	Benign	0.027	T;.
Eigen	Benign	-0.84
Eigen_PC	Benign	-0.83
FATHMM_MKL	Benign	0.076	N
LIST_S2	Benign	0.64	T;T
M_CAP	Benign	0.0075	T
MetaRNN	Benign	0.0029	T;T
MetaSVM	Benign	-0.94	T
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.37	T
Sift4G	Benign	0.37	T;T
Vest4		0.23
MutPred		0.085		Gain of relative solvent accessibility (P = 0.1012);Gain of relative solvent accessibility (P = 0.1012);
MVP		0.14
MPC		0.13
ClinPred		0.0077	T
GERP RS		0.24
Varity_R		0.030
gMVP		0.063

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

Other links and lift over

dbSNP: rs117292623; hg19: chr18-13015389; COSMIC: COSV100382505;