18-13029736-A-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.1124A>G(p.His375Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000143 in 1,399,234 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: CEP192 NM_032142.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.00

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=0.08171585).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CEP192	NM_032142.4	c.1124A>G	p.His375Arg	missense_variant	10/45	ENST00000506447.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CEP192	ENST00000506447.5	c.1124A>G	p.His375Arg	missense_variant	10/45	5	NM_032142.4	P1
CEP192	ENST00000513432.5	c.791A>G	p.His264Arg	missense_variant, NMD_transcript_variant	7/39	1
CEP192	ENST00000325971.12	c.-92A>G		5_prime_UTR_variant	10/44	5
CEP192	ENST00000589596.5	c.968-8779A>G		intron_variant		2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000143 AC: 2 AN: 1399234 Hom.: 0 Cov.: 31 AF XY: 0.00000145 AC XY: 1 AN XY: 690102

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: 0.00000185

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

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

Sep 26, 2023

The c.1124A>G (p.H375R) alteration is located in exon 10 (coding exon 9) of the CEP192 gene. This alteration results from a A to G substitution at nucleotide position 1124, causing the histidine (H) at amino acid position 375 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	0.076
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
Cadd	Benign	10
Dann	Benign	0.80
Eigen	Benign	-0.97
Eigen_PC	Benign	-0.93
FATHMM_MKL	Benign	0.26	N
LIST_S2	Benign	0.43	T
M_CAP	Benign	0.0097	T
MetaRNN	Benign	0.082	T
MetaSVM	Benign	-0.95	T
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.72	N
REVEL	Benign	0.075
Sift	Uncertain	0.020	D
Sift4G	Benign	0.079	T
Vest4		0.21
MutPred		0.24		Gain of helix (P = 0.062);
MVP		0.12
MPC		0.14
ClinPred		0.15	T
GERP RS		3.8
Varity_R		0.070
gMVP		0.059

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: chr18-13029735;