6-99561389-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_005190.4(CCNC):​c.272T>G​(p.Val91Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

CCNC
NM_005190.4 missense

Scores

10
7
2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.13
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]
TSTD3 (HGNC:40910): (thiosulfate sulfurtransferase like domain containing 3)

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.859

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CCNCNM_005190.4 linkuse as main transcriptc.272T>G p.Val91Gly missense_variant 4/12 ENST00000520429.6 NP_005181.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CCNCENST00000520429.6 linkuse as main transcriptc.272T>G p.Val91Gly missense_variant 4/121 NM_005190.4 ENSP00000428982 P1P24863-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
28
GnomAD4 genome
Cov.:
32

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 submitterclinical testingAmbry GeneticsJun 17, 2024The c.272T>G (p.V91G) alteration is located in exon 4 (coding exon 4) of the CCNC gene. This alteration results from a T to G substitution at nucleotide position 272, causing the valine (V) at amino acid position 91 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
Pathogenic
0.92
BayesDel_addAF
Pathogenic
0.31
D
BayesDel_noAF
Pathogenic
0.21
CADD
Pathogenic
29
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.48
T;T;T;.;T;.;T;.;T;.;T
Eigen
Pathogenic
0.85
Eigen_PC
Pathogenic
0.83
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Pathogenic
0.99
D;D;.;.;D;D;D;D;D;D;D
M_CAP
Uncertain
0.14
D
MetaRNN
Pathogenic
0.86
D;D;D;D;D;D;D;D;D;D;D
MetaSVM
Benign
-0.65
T
MutationAssessor
Uncertain
2.8
M;.;.;.;.;.;.;.;.;.;.
MutationTaster
Benign
1.0
D;D;D;D;D;D;D
PrimateAI
Pathogenic
0.87
D
PROVEAN
Pathogenic
-5.3
D;D;D;D;D;D;D;D;.;D;D
REVEL
Uncertain
0.61
Sift
Uncertain
0.0020
D;D;D;D;D;D;D;D;.;D;D
Sift4G
Uncertain
0.0020
D;D;D;D;D;D;D;D;D;.;D
Polyphen
0.92
P;.;.;.;.;.;.;.;.;.;.
Vest4
0.57
MutPred
0.59
Loss of stability (P = 0.0896);Loss of stability (P = 0.0896);Loss of stability (P = 0.0896);.;.;.;Loss of stability (P = 0.0896);.;Loss of stability (P = 0.0896);.;Loss of stability (P = 0.0896);
MVP
0.75
MPC
2.4
ClinPred
1.0
D
GERP RS
5.8
Varity_R
0.95
gMVP
0.91

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.

Other links and lift over

hg19: chr6-100009265; API