6-99546446-C-A

Variant names:

• chr6-99546446-C-A
• NM_005190.4:c.627G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005190.4(CCNC):​c.627G>T​(p.Gln209His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 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: 2.26
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19836992).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005190.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCNC	NM_005190.4	MANE Select	c.627G>T	p.Gln209His	missense	Exon 10 of 12	NP_005181.2	P24863-1
	CCNC	NM_001363537.2		c.627G>T	p.Gln209His	missense	Exon 10 of 13	NP_001350466.1	E5RFK5
	CCNC	NM_001013399.2		c.372G>T	p.Gln124His	missense	Exon 10 of 12	NP_001013417.1	P24863-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCNC	ENST00000520429.6	TSL:1 MANE Select	c.627G>T	p.Gln209His	missense	Exon 10 of 12	ENSP00000428982.1	P24863-1
	CCNC	ENST00000369220.8	TSL:1	c.624G>T	p.Gln208His	missense	Exon 10 of 12	ENSP00000358222.4	J3KP90
	CCNC	ENST00000326298.8	TSL:1	n.*106G>T		non_coding_transcript_exon	Exon 11 of 13	ENSP00000319027.4	G5E954

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.41
BayesDel_addAF	Benign	-0.043	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	16
DANN	Benign	0.97
DEOGEN2	Benign	0.29	T
Eigen	Benign	-0.56
Eigen_PC	Benign	-0.42
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.030	D
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.94	L
PhyloP100		2.3
PrimateAI	Pathogenic	0.91	D
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.20
Sift	Benign	0.18	T
Sift4G	Benign	0.14	T
Polyphen		0.010	B
Vest4		0.64
MutPred		0.43		Loss of catalytic residue at Q209 (P = 0.033)
MVP		0.56
MPC		0.92
ClinPred		0.25	T
GERP RS		-0.70
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.7
Varity_R		0.19
gMVP		0.68
Mutation Taster		=31/69	disease causing

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

Other links and lift over

hg19: chr6-99994322;