Variant 6-41940419-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_001760.5(CCND3):c.365A>G(p.Glu122Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00018 in 1,613,606 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000073 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00019 ( 1 hom. )

Consequence

CCND3
NM_001760.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.21

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.3537482).

BS2

High AC in GnomAd at 11 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCND3	NM_001760.5 linkuse as main transcript	c.365A>G	p.Glu122Gly	missense_variant	2/5	ENST00000372991.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCND3	ENST00000372991.9 linkuse as main transcript	c.365A>G	p.Glu122Gly	missense_variant	2/5	1	NM_001760.5	P1	P30281-1

Frequencies

GnomAD3 genomes

AF:

0.0000725

AC:

AN:

151720

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000485

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000133

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000875

AC:

AN:

251426

Hom.:

AF XY:

0.0000809

AC XY:

AN XY:

135914

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000176

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000191

AC:

279

AN:

1461886

Hom.:

Cov.:

AF XY:

0.000172

AC XY:

125

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.0000896

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000237

Gnomad4 OTH exome

AF:

0.000199

GnomAD4 genome

AF:

0.0000725

AC:

AN:

151720

Hom.:

Cov.:

AF XY:

0.0000675

AC XY:

AN XY:

74110

show subpopulations

Gnomad4 AFR

AF:

0.0000485

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000133

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000197

Hom.:

Bravo

AF:

0.0000907

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.0000494

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000237

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 07, 2021

The c.365A>G (p.E122G) alteration is located in exon 2 (coding exon 2) of the CCND3 gene. This alteration results from a A to G substitution at nucleotide position 365, causing the glutamic acid (E) at amino acid position 122 to be replaced by a glycine (G). 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

0.33

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.30

Cadd

Pathogenic

Dann

Uncertain

1.0

DEOGEN2

Benign

0.21

T;.;T;.;.;T;T;.

Eigen

Uncertain

0.33

Eigen_PC

Uncertain

0.37

FATHMM_MKL

Uncertain

0.96

LIST_S2

Pathogenic

0.98

D;.;D;D;D;D;D;T

M_CAP

Benign

0.036

MetaRNN

Benign

0.35

T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.68

MutationAssessor

Uncertain

2.2

M;.;.;.;.;.;.;.

MutationTaster

Benign

1.0

D;D;D;D;D;D;D

PrimateAI

Uncertain

0.64

PROVEAN

Pathogenic

-5.8

D;D;D;D;D;.;D;D

REVEL

Benign

0.26

Sift

Uncertain

0.0020

D;D;D;D;D;.;D;D

Sift4G

Benign

0.067

T;T;D;T;T;T;T;.

Polyphen

0.99

D;.;D;.;.;.;.;.

Vest4

0.75

MVP

0.51

MPC

1.7

ClinPred

0.39

GERP RS

4.8

Varity_R

0.85

gMVP

0.32

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over