Variant 5-163441320-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_004060.4(CCNG1):c.507G>C(p.Leu169Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000845 in 1,613,404 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00048 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00088 ( 1 hom. )

Consequence

CCNG1
NM_004060.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.322

Variant links:

Genes affected

CCNG1 (HGNC:1592): (cyclin G1) The eukaryotic cell cycle is governed by cyclin-dependent protein kinases (CDKs) whose activities are regulated by cyclins and CDK inhibitors. The protein encoded by this gene is a member of the cyclin family and contains the cyclin box. The encoded protein lacks the protein destabilizing (PEST) sequence that is present in other family members. Transcriptional activation of this gene can be induced by tumor protein p53. Two transcript variants encoding the same protein have been identified for this gene. [provided by RefSeq, Jul 2008]

CCNG1 links:

CCNG1 (HGNC:):

CCNG1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.07738039).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCNG1	NM_004060.4 linkuse as main transcript	c.507G>C	p.Leu169Phe	missense_variant	3/7	ENST00000340828.7	NP_004051.1	P51959-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCNG1	ENST00000340828.7 linkuse as main transcript	c.507G>C	p.Leu169Phe	missense_variant	3/7	1	NM_004060.4	ENSP00000344635.2		P51959-1
CCNG1	ENST00000510664.5 linkuse as main transcript	c.123G>C	p.Leu41Phe	missense_variant	3/7	5		ENSP00000422379.1		E7ERZ1

Frequencies

GnomAD3 genomes

AF:

0.000480

AC:

AN:

152168

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

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:

0.000941

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000431

AC:

108

AN:

250670

Hom.:

AF XY:

0.000391

AC XY:

AN XY:

135572

show subpopulations

Gnomad AFR exome

AF:

0.0000617

Gnomad AMR exome

AF:

0.0000870

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000464

Gnomad NFE exome

AF:

0.000891

Gnomad OTH exome

AF:

0.000328

GnomAD4 exome

AF:

0.000883

AC:

1290

AN:

1461236

Hom.:

Cov.:

AF XY:

0.000861

AC XY:

626

AN XY:

726902

show subpopulations

Gnomad4 AFR exome

AF:

0.000120

Gnomad4 AMR exome

AF:

0.000157

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000131

Gnomad4 NFE exome

AF:

0.00111

Gnomad4 OTH exome

AF:

0.000547

GnomAD4 genome

AF:

0.000480

AC:

AN:

152168

Hom.:

Cov.:

AF XY:

0.000430

AC XY:

AN XY:

74348

show subpopulations

Gnomad4 AFR

AF:

0.000169

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000941

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000835

Hom.:

Bravo

AF:

0.000499

TwinsUK

AF:

0.00135

AC:

ALSPAC

AF:

0.00156

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000581

AC:

ExAC

AF:

0.000404

AC:

EpiCase

AF:

0.000763

EpiControl

AF:

0.000533

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

Sep 15, 2021

The c.507G>C (p.L169F) alteration is located in exon 3 (coding exon 2) of the CCNG1 gene. This alteration results from a G to C substitution at nucleotide position 507, causing the leucine (L) at amino acid position 169 to be replaced by a phenylalanine (F). 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

0.086

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.32

.;T;T;.;.

Eigen

Benign

-0.17

Eigen_PC

Benign

-0.17

FATHMM_MKL

Uncertain

0.81

LIST_S2

Benign

0.82

T;T;.;T;T

M_CAP

Benign

0.013

MetaRNN

Benign

0.077

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.4

.;M;M;.;.

PrimateAI

Benign

0.35

PROVEAN

Benign

-1.9

N;N;N;N;N

REVEL

Benign

0.061

Sift

Uncertain

0.014

D;D;D;D;D

Sift4G

Benign

0.085

T;T;T;T;T

Polyphen

0.74

.;P;P;.;.

Vest4

0.44

MutPred

0.31

.;Loss of loop (P = 0.1242);Loss of loop (P = 0.1242);.;.;

MVP

0.73

MPC

0.22

ClinPred

0.051

GERP RS

0.80

Varity_R

0.14

gMVP

0.35

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