rs147068728

Variant names:

• chr19-40224499-C-A
• rs147068728
• NM_024877.4:c.502G>T

Your query was ambiguous. Multiple possible variants found:

• chr19-40224499-C-A
• chr19-40224499-C-T

Variant summary

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

The NM_024877.4(CCNP):​c.502G>T​(p.Val168Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,808 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V168M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CCNP NM_024877.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.79
• 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]

ENSG00000309303 (HGNC:):

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=0.09359163).

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.502G>T	p.Val168Leu	missense	Exon 3 of 5	NP_079153.2	Q9H8S5-1
	CCNP	NM_001411133.1		c.502G>T	p.Val168Leu	missense	Exon 3 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.502G>T	p.Val168Leu	missense	Exon 3 of 5	ENSP00000396755.2	Q9H8S5-1
	CCNP	ENST00000599263.6	TSL:5	c.502G>T	p.Val168Leu	missense	Exon 3 of 6	ENSP00000470643.2	M0QZM5
	CCNP	ENST00000921917.1		c.412G>T	p.Val138Leu	missense	Exon 2 of 4	ENSP00000591976.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461808 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 727208

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53388

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111986

Other (OTH) AF: 0.0000166 AC: 1 AN: 60390

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	17
DANN	Benign	0.93
DEOGEN2	Benign	0.0027	T
Eigen	Benign	-0.40
Eigen_PC	Benign	-0.19
FATHMM_MKL	Benign	0.51	D
LIST_S2	Benign	0.60	T
M_CAP	Benign	0.0058	T
MetaRNN	Benign	0.094	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	-1.0	N
PhyloP100		1.8
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	0.73	N
REVEL	Benign	0.059
Sift	Benign	1.0	T
Sift4G	Benign	0.65	T
Vest4		0.32
MutPred		0.45		Gain of relative solvent accessibility (P = 0.0289)
MVP		0.39
MPC		0.99
ClinPred		0.61	D
GERP RS		3.8
PromoterAI		-0.036	Neutral
Varity_R		0.045
gMVP		0.035
Mutation Taster		=92/8	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: rs147068728; hg19: chr19-40730406;