6-99551877-T-A

Position:

• chr6-99551877-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005190.4(CCNC):​c.365A>T​(p.Tyr122Phe) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• Consequence: CCNC NM_005190.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.72

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)

ACMG classification

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=0.24466434).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCNC	NM_005190.4	c.365A>T	p.Tyr122Phe	missense_variant	6/12	ENST00000520429.6	NP_005181.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCNC	ENST00000520429.6	c.365A>T	p.Tyr122Phe	missense_variant	6/12	1	NM_005190.4	ENSP00000428982	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 24

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 01, 2024

The c.365A>T (p.Y122F) alteration is located in exon 6 (coding exon 6) of the CCNC gene. This alteration results from a A to T substitution at nucleotide position 365, causing the tyrosine (Y) at amino acid position 122 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	0.069
BayesDel_addAF	Benign	-0.071	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	22
DANN	Benign	0.95
DEOGEN2	Benign	0.29	T;T;T;.;T;.;T;.;T;.
Eigen	Benign	0.064
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.95	D;D;.;.;D;D;D;D;D;D
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.24	T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.63	N;.;.;.;.;.;.;.;.;.
MutationTaster	Benign	1.0	D;D;D;D;D;D
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	-1.2	N;N;N;N;N;N;N;N;.;N
REVEL	Benign	0.15
Sift	Benign	0.22	T;T;T;T;T;T;T;T;.;T
Sift4G	Benign	0.47	T;T;T;T;T;T;T;T;T;.
Polyphen		0.0	B;.;.;.;.;.;.;.;.;.
Vest4		0.23
MutPred		0.44		Loss of methylation at K117 (P = 0.0849);Loss of methylation at K117 (P = 0.0849);Loss of methylation at K117 (P = 0.0849);.;.;.;Loss of methylation at K117 (P = 0.0849);.;Loss of methylation at K117 (P = 0.0849);.;
MVP		0.36
MPC		0.90
ClinPred		0.63	D
GERP RS		5.9
Varity_R		0.40
gMVP		0.40

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: chr6-99999753;