NM_032142.4:c.7346G>C

Variant names:

• chr18-13116433-G-C
• rs1786263
• NM_032142.4:c.7346G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_032142.4(CEP192):​c.7346G>C​(p.Arg2449Pro) 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. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: CEP192 NM_032142.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.555
• Publications: 61 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11537179).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032142.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP192	NM_032142.4	MANE Select	c.7346G>C	p.Arg2449Pro	missense	Exon 43 of 45	NP_115518.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP192	ENST00000506447.5	TSL:5 MANE Select	c.7346G>C	p.Arg2449Pro	missense	Exon 43 of 45	ENSP00000427550.1
	CEP192	ENST00000511820.6	TSL:1	c.5960G>C	p.Arg1987Pro	missense	Exon 33 of 35	ENSP00000467038.1
	CEP192	ENST00000510237.5	TSL:1	n.*204G>C		non_coding_transcript_exon	Exon 33 of 35	ENSP00000423147.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 38

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	14
DANN	Benign	0.91
DEOGEN2	Benign	0.0035	T
Eigen	Benign	-0.81
Eigen_PC	Benign	-0.59
FATHMM_MKL	Benign	0.36	N
LIST_S2	Benign	0.14	T
M_CAP	Benign	0.0090	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.0	T
PhyloP100		0.56
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	2.9	N
REVEL	Benign	0.11
Sift	Benign	0.28	T
Sift4G	Benign	0.15	T
Vest4		0.20
MutPred		0.40		Gain of loop (P = 0.0166)
MVP		0.18
MPC		0.14
ClinPred		0.87	D
GERP RS		4.8
Varity_R		0.13
gMVP		0.37
Mutation Taster		=95/5	polymorphism

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

Other links and lift over

dbSNP: rs1786263; hg19: chr18-13116432;