rs7011

chr14-102348705-C-Gchr14-102348705-C-T

Variant summary

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

The NM_032630.3(CINP):c.491G>C(p.Arg164Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. R164H) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CINP NM_032630.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.667

Genes affected

CINP (HGNC:23789): (cyclin dependent kinase 2 interacting protein) The protein encoded by this gene is reported to be a component of the DNA replication complex as well as a genome-maintenance protein. It may interact with proteins important for replication initiation and has been shown to bind chromatin at the G1 phase of the cell cycle and dissociate from chromatin with replication initiation. It may also serve to regulate checkpoint signaling as part of the DNA damage response. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2016]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CINP	NM_032630.3	c.491G>C	p.Arg164Pro	missense_variant	5/5	ENST00000216756.11
CINP	NM_001320046.2	c.*4G>C		3_prime_UTR_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CINP	ENST00000216756.11	c.491G>C	p.Arg164Pro	missense_variant	5/5	1	NM_032630.3	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 42

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.81
BayesDel_addAF	Uncertain	0.089	D
BayesDel_noAF	Benign	-0.11
Cadd	Benign	19
Dann	Uncertain	0.99
DEOGEN2	Benign	0.12	T;.
Eigen	Benign	0.045
Eigen_PC	Benign	-0.043
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.84	T;T
M_CAP	Benign	0.064	D
MetaRNN	Uncertain	0.69	D;D
MetaSVM	Benign	-0.43	T
MutationAssessor	Uncertain	2.5	M;.
MutationTaster	Benign	0.30	P;P;P
PrimateAI	Benign	0.22	T
PROVEAN	Uncertain	-4.1	D;D
REVEL	Benign	0.27
Sift	Uncertain	0.014	D;D
Sift4G	Uncertain	0.015	D;D
Polyphen		0.99	D;.
Vest4		0.52
MutPred		0.34		Gain of catalytic residue at E169 (P = 0.0042);.;
MVP		0.73
MPC		0.65
ClinPred		0.98	D
GERP RS		2.8
Varity_R		0.63
gMVP		0.63

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

LitVar

Other links and lift over

dbSNP: rs7011; hg19: chr14-102815042;