15-55359643-G-T

Position:

• chr15-55359643-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001204450.2(CCPG1):​c.2130C>A​(p.Asn710Lys) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CCPG1 NM_001204450.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.61

Genes affected

CCPG1 (HGNC:24227): (cell cycle progression 1) Involved in positive regulation of cell cycle and positive regulation of cell population proliferation. Predicted to be integral component of membrane. Predicted to be active in membrane. [provided by Alliance of Genome Resources, Apr 2022]

DNAAF4-CCPG1 (HGNC:):

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=0.075440615).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCPG1	NM_001204450.2	c.2130C>A	p.Asn710Lys	missense_variant	8/9	ENST00000442196.8	NP_001191379.1
DNAAF4-CCPG1	NR_037923.1	n.3547C>A		non_coding_transcript_exon_variant	15/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCPG1	ENST00000442196.8	c.2130C>A	p.Asn710Lys	missense_variant	8/9	2	NM_001204450.2	ENSP00000403400	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

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

Apr 08, 2024

The c.2130C>A (p.N710K) alteration is located in exon 8 (coding exon 7) of the CCPG1 gene. This alteration results from a C to A substitution at nucleotide position 2130, causing the asparagine (N) at amino acid position 710 to be replaced by a lysine (K). 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	0.23
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0093	.;T;.;T
Eigen	Benign	-0.30
Eigen_PC	Benign	-0.11
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Uncertain	0.89	D;.;T;D
M_CAP	Benign	0.0061	T
MetaRNN	Benign	0.075	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N;N;.;N
MutationTaster	Benign	0.99	N;N;N;N
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.80	N;N;N;N
REVEL	Benign	0.021
Sift	Uncertain	0.010	D;D;T;D
Sift4G	Uncertain	0.024	D;D;T;D
Polyphen		0.095, 0.066	.;B;B;B
Vest4		0.19
MutPred		0.29		Gain of ubiquitination at N710 (P = 0.0267);Gain of ubiquitination at N710 (P = 0.0267);.;Gain of ubiquitination at N710 (P = 0.0267);
MVP		0.043
MPC		0.16
ClinPred		0.32	T
GERP RS		3.9
Varity_R		0.070
gMVP		0.33

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: chr15-55651841;