18-13015383-T-G

Variant summary

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

The NM_032142.4(CEP192):c.575T>G(p.Leu192Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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)
• Consequence: CEP192 NM_032142.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.662

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=0.1742326).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CEP192	NM_032142.4	c.575T>G	p.Leu192Arg	missense_variant	6/45	ENST00000506447.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CEP192	ENST00000506447.5	c.575T>G	p.Leu192Arg	missense_variant	6/45	5	NM_032142.4	P1
CEP192	ENST00000513432.5	c.242T>G	p.Leu81Arg	missense_variant, NMD_transcript_variant	3/39	1
CEP192	ENST00000589596.5	c.575T>G	p.Leu192Arg	missense_variant	6/18	2
CEP192	ENST00000325971.12	c.-641T>G		5_prime_UTR_variant	6/44	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

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

Dec 07, 2023

The c.575T>G (p.L192R) alteration is located in exon 6 (coding exon 5) of the CEP192 gene. This alteration results from a T to G substitution at nucleotide position 575, causing the leucine (L) at amino acid position 192 to be replaced by an arginine (R). 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	0.11
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
Cadd	Benign	21
Dann	Uncertain	1.0
DEOGEN2	Benign	0.020	T;.
Eigen	Benign	0.17
Eigen_PC	Benign	0.14
FATHMM_MKL	Benign	0.69	D
LIST_S2	Benign	0.64	T;T
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.17	T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	D;N
PrimateAI	Benign	0.33	T
Sift4G	Benign	0.083	T;D
Vest4		0.37
MutPred		0.25		Gain of ubiquitination at K189 (P = 0.047);Gain of ubiquitination at K189 (P = 0.047);
MVP		0.45
MPC		0.41
ClinPred		0.80	D
GERP RS		4.1
Varity_R		0.17
gMVP		0.037

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr18-13015382;