NM_024877.4:c.527G>C

Variant names:

• chr19-40223533-C-G
• NM_024877.4:c.527G>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_024877.4(CCNP):​c.527G>C​(p.Cys176Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CCNP NM_024877.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.22
• Publications: 0 publications found

Genes affected

CCNP (HGNC:25805): (cyclin P) Predicted to enable cyclin-dependent protein serine/threonine kinase regulator activity. Predicted to be involved in mitotic cell cycle phase transition and regulation of cyclin-dependent protein serine/threonine kinase activity. Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.31011367).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024877.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCNP	NM_024877.4	MANE Select	c.527G>C	p.Cys176Ser	missense	Exon 4 of 5	NP_079153.2	Q9H8S5-1
	CCNP	NM_001411133.1		c.527G>C	p.Cys176Ser	missense	Exon 4 of 6	NP_001398062.1	M0QZM5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCNP	ENST00000430325.7	TSL:2 MANE Select	c.527G>C	p.Cys176Ser	missense	Exon 4 of 5	ENSP00000396755.2	Q9H8S5-1
	CCNP	ENST00000599263.6	TSL:5	c.527G>C	p.Cys176Ser	missense	Exon 4 of 6	ENSP00000470643.2	M0QZM5
	CCNP	ENST00000921917.1		c.437G>C	p.Cys146Ser	missense	Exon 3 of 4	ENSP00000591976.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.48
BayesDel_addAF	Benign	-0.081	T
BayesDel_noAF	Benign	-0.35
CADD	Uncertain	24
DANN	Benign	0.76
DEOGEN2	Benign	0.016	T
Eigen	Benign	-0.25
Eigen_PC	Benign	-0.16
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.41	T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.31	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.1	L
PhyloP100		4.2
PrimateAI	Uncertain	0.73	T
PROVEAN	Uncertain	-3.0	D
REVEL	Benign	0.19
Sift	Benign	0.39	T
Sift4G	Uncertain	0.052	T
Vest4		0.81
MutPred		0.63		Gain of disorder (P = 0.0078)
MVP		0.47
MPC		0.87
ClinPred		0.27	T
GERP RS		3.9
Varity_R		0.19
gMVP		0.29
Mutation Taster		=81/19	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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

hg19: chr19-40729440;