6-41936044-A-G

Position:

• chr6-41936044-A-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001760.5(CCND3):​c.775T>C​(p.Ser259Pro) 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. 13/17 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. S259A) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CCND3 NM_001760.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.143

Genes affected

CCND3 (HGNC:1585): (cyclin D3) The protein encoded by this gene belongs to the highly conserved cyclin family, whose members are characterized by a dramatic periodicity in protein abundance through the cell cycle. Cyclins function as regulators of CDK kinases. Different cyclins exhibit distinct expression and degradation patterns which contribute to the temporal coordination of each mitotic event. This cyclin forms a complex with and functions as a regulatory subunit of CDK4 or CDK6, whose activtiy is required for cell cycle G1/S transition. This protein has been shown to interact with and be involved in the phosphorylation of tumor suppressor protein Rb. The CDK4 activity associated with this cyclin was reported to be necessary for cell cycle progression through G2 phase into mitosis after UV radiation. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2008]

CCND3 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05670762).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCND3	NM_001760.5	c.775T>C	p.Ser259Pro	missense_variant	5/5	ENST00000372991.9	NP_001751.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCND3	ENST00000372991.9	c.775T>C	p.Ser259Pro	missense_variant	5/5	1	NM_001760.5	ENSP00000362082.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 48

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.096
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	9.0
DANN	Benign	0.95
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.072	N
LIST_S2	Benign	0.19	T
M_CAP	Benign	0.0087	T
MetaRNN	Benign	0.057	T
MetaSVM	Benign	-0.92	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.036
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0010	D
Vest4		0.12
MutPred		0.19		Gain of glycosylation at L132 (P = 0.0208);
MVP		0.22
ClinPred		0.12	T
GERP RS		0.19

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: rs1051130; hg19: chr6-41903782;