NM_024877.4:c.877C>T

Variant names:

• chr19-40223099-G-A
• NM_024877.4:c.877C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_024877.4(CCNP):​c.877C>T​(p.Pro293Ser) 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. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P293R) has been classified 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: 0.298
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.051033974).

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.877C>T	p.Pro293Ser	missense	Exon 5 of 5	NP_079153.2	Q9H8S5-1
	CCNP	NM_001411133.1		c.824+53C>T		intron	N/A	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.877C>T	p.Pro293Ser	missense	Exon 5 of 5	ENSP00000396755.2	Q9H8S5-1
	CCNP	ENST00000921917.1		c.787C>T	p.Pro263Ser	missense	Exon 4 of 4	ENSP00000591976.1
	CCNP	ENST00000921918.1		c.631C>T	p.Pro211Ser	missense	Exon 3 of 3	ENSP00000591977.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

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	Benign	0.098
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	15
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0049	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.095	N
LIST_S2	Benign	0.47	T
M_CAP	Benign	0.0079	T
MetaRNN	Benign	0.051	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L
PhyloP100		0.30
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.29	N
REVEL	Benign	0.026
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Vest4		0.039
MutPred		0.28		Gain of phosphorylation at P293 (P = 0.0146)
MVP		0.13
MPC		0.65
ClinPred		0.075	T
GERP RS		-0.58
Varity_R		0.033
gMVP		0.20
Mutation Taster		=98/2	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

hg19: chr19-40729006;