18-13018559-C-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.869C>T(p.Ser290Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000072 in 1,389,838 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: CEP192 NM_032142.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.891

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=0.1742911).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CEP192	NM_032142.4	c.869C>T	p.Ser290Phe	missense_variant	8/45	ENST00000506447.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CEP192	ENST00000506447.5	c.869C>T	p.Ser290Phe	missense_variant	8/45	5	NM_032142.4	P1
CEP192	ENST00000513432.5	c.536C>T	p.Ser179Phe	missense_variant, NMD_transcript_variant	5/39	1
CEP192	ENST00000589596.5	c.869C>T	p.Ser290Phe	missense_variant	8/18	2
CEP192	ENST00000325971.12	c.-347C>T		5_prime_UTR_variant	8/44	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.20e-7 AC: 1 AN: 1389838 Hom.: 0 Cov.: 27 AF XY: 0.00000146 AC XY: 1 AN XY: 685752

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000174

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 18, 2021

The c.869C>T (p.S290F) alteration is located in exon 8 (coding exon 7) of the CEP192 gene. This alteration results from a C to T substitution at nucleotide position 869, causing the serine (S) at amino acid position 290 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
Cadd	Benign	21
Dann	Uncertain	1.0
DEOGEN2	Benign	0.0028	T;.
Eigen	Benign	-0.13
Eigen_PC	Benign	-0.25
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.60	T;T
M_CAP	Benign	0.028	D
MetaRNN	Benign	0.17	T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.30	T
Sift4G	Uncertain	0.0090	D;T
Vest4		0.28
MutPred		0.22		Loss of phosphorylation at S290 (P = 0.0089);Loss of phosphorylation at S290 (P = 0.0089);
MVP		0.44
MPC		0.51
ClinPred		0.80	D
GERP RS		2.9
Varity_R		0.093
gMVP		0.17

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr18-13018558;