6-99558419-T-TA

Position:

• chr6-99558419-T-TA

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BS1_Supporting BS2

The ENST00000482541.2(CCNC):​c.423_424insT​(p.Ser142Ter) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0235 in 1,141,226 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as not provided (no stars).

• Frequency:
  • Genomes: 𝑓 0.0012 (0 hom., cov: 32)
  • Exomes 𝑓: 0.027 (0 hom.)
• Consequence: CCNC ENST00000482541.2 frameshift
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: -0.0120

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 Likely_benign. Variant got -5 ACMG points.

• BS1: Variant frequency is greater than expected in population sas. gnomad4_exome allele frequency = 0.0268 (26699/997338) while in subpopulation SAS AF= 0.0425 (2466/58010). AF 95% confidence interval is 0.0411. There are 0 homozygotes in gnomad4_exome. There are 13565 alleles in male gnomad4_exome subpopulation. Median coverage is 0. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
• BS2: High AC in GnomAd4 at 168 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCNC	NM_005190.4	c.346+77_346+78insT		intron_variant		ENST00000520429.6	NP_005181.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCNC	ENST00000520429.6	c.346+77_346+78insT		intron_variant		1	NM_005190.4	ENSP00000428982	P1

Frequencies

GnomAD3 genomes AF: 0.00115 AC: 166 AN: 143854 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00185

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00167

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000794

Gnomad SAS AF: 0.00240

Gnomad FIN AF: 0.00138

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000582

Gnomad OTH AF: 0.00203

GnomAD4 exome AF: 0.0268 AC: 26699 AN: 997338 Hom.: 0 Cov.: 0 AF XY: 0.0272 AC XY: 13565 AN XY: 499186

Gnomad4 AFR exome AF: 0.0274

Gnomad4 AMR exome AF: 0.0291

Gnomad4 ASJ exome AF: 0.0271

Gnomad4 EAS exome AF: 0.0190

Gnomad4 SAS exome AF: 0.0425

Gnomad4 FIN exome AF: 0.0223

Gnomad4 NFE exome AF: 0.0261

Gnomad4 OTH exome AF: 0.0261

GnomAD4 genome AF: 0.00117 AC: 168 AN: 143888 Hom.: 0 Cov.: 32 AF XY: 0.00123 AC XY: 86 AN XY: 69840

Gnomad4 AFR AF: 0.00192

Gnomad4 AMR AF: 0.00167

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000797

Gnomad4 SAS AF: 0.00219

Gnomad4 FIN AF: 0.00138

Gnomad4 NFE AF: 0.000582

Gnomad4 OTH AF: 0.00202

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

Submissions by phenotype

CIC-rearranged sarcoma Other:1

not provided, no classification provided

literature only

Children's Cancer Therapy Development Institute

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Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs761291714; hg19: chr6-100006295;