Variant 6-99545143-T-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_005190.4(CCNC):c.766A>C(p.Lys256Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,456,276 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

CCNC
NM_005190.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.01

Variant links:

Genes affected

CCNC (HGNC:1581): (cyclin C) The protein encoded by this gene is a member of the cyclin family of proteins. The encoded protein interacts with cyclin-dependent kinase 8 and induces the phophorylation of the carboxy-terminal domain of the large subunit of RNA polymerase II. The level of mRNAs for this gene peaks in the G1 phase of the cell cycle. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

CCNC links:

TSTD3 (HGNC:40910): (thiosulfate sulfurtransferase like domain containing 3)

TSTD3 links:

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ACMG classification

Classification made for transcript

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	Protein	UniProt
CCNC	NM_005190.4 linkuse as main transcript	c.766A>C	p.Lys256Gln	missense_variant	11/12	ENST00000520429.6	NP_005181.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCNC	ENST00000520429.6 linkuse as main transcript	c.766A>C	p.Lys256Gln	missense_variant	11/12	1	NM_005190.4	ENSP00000428982	P1	P24863-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.87e-7

AC:

AN:

1456276

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

724922

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Jan 08, 2024

The c.766A>C (p.K256Q) alteration is located in exon 11 (coding exon 11) of the CCNC gene. This alteration results from a A to C substitution at nucleotide position 766, causing the lysine (K) at amino acid position 256 to be replaced by a glutamine (Q). 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

0.30

BayesDel_addAF

Benign

0.0041

BayesDel_noAF

Benign

-0.23

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.64

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

Eigen

Pathogenic

0.85

Eigen_PC

Pathogenic

0.82

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Pathogenic

0.97

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

M_CAP

Uncertain

0.12

MetaRNN

Uncertain

0.59

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

MetaSVM

Benign

-0.49

MutationAssessor

Uncertain

2.7

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

MutationTaster

Benign

1.0

D;D;D;D;D;D

PrimateAI

Uncertain

0.72

PROVEAN

Uncertain

-3.1

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

REVEL

Uncertain

0.30

Sift

Uncertain

0.0040

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

Sift4G

Uncertain

0.0060

D;D;T;D;T;D;T

Polyphen

1.0

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

Vest4

0.48

MutPred

0.32

Loss of methylation at K256 (P = 0.0122);.;Loss of methylation at K256 (P = 0.0122);.;.;.;Loss of methylation at K256 (P = 0.0122);

MVP

0.61

MPC

2.1

ClinPred

0.98

GERP RS

5.9

Varity_R

0.55

gMVP

0.73

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over