rs1786263

chr18-13116433-G-Achr18-13116433-G-Cchr18-13116433-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_032142.4(CEP192):c.7346G>A(p.Arg2449Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,459,796 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R2449L) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: CEP192 NM_032142.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.555

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09485409).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CEP192	NM_032142.4	c.7346G>A	p.Arg2449Gln	missense_variant	43/45	ENST00000506447.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CEP192	ENST00000506447.5	c.7346G>A	p.Arg2449Gln	missense_variant	43/45	5	NM_032142.4	P1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD3 exomes AF: 0.00000402 AC: 1 AN: 248966 Hom.: 0 AF XY: 0.00000744 AC XY: 1 AN XY: 134488

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000548

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000206 AC: 3 AN: 1459796 Hom.: 0 Cov.: 38 AF XY: 0.00000275 AC XY: 2 AN XY: 726026

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.62
Cadd	Benign	14
Dann	Benign	0.96
Eigen	Benign	-0.69
Eigen_PC	Benign	-0.52
FATHMM_MKL	Benign	0.56	D
LIST_S2	Benign	0.61	T;T
M_CAP	Benign	0.0076	T
MetaRNN	Benign	0.095	T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	P;P;P
PrimateAI	Benign	0.43	T
PROVEAN	Benign	0.33	N;.
REVEL	Benign	0.091
Sift	Benign	0.30	T;.
Sift4G	Benign	0.26	T;T
Vest4		0.17
MutPred		0.31		.;Loss of methylation at R1974 (P = 0.0455);
MVP		0.29
MPC		0.11
ClinPred		0.18	T
GERP RS		4.8
Varity_R		0.029
gMVP		0.25

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: rs1786263; hg19: chr18-13116432;