rs12555

Positions:

• chr7-56063139-T-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000275603.9(CCT6A):​c.*54T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0272 in 1,221,244 control chromosomes in the GnomAD database, including 787 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.038 (155 hom., cov: 32)
  • Exomes 𝑓: 0.026 (632 hom.)
• Consequence: CCT6A ENST00000275603.9 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.03

Genes affected

CCT6A (HGNC:1620): (chaperonin containing TCP1 subunit 6A) The protein encoded by this gene is a molecular chaperone that is a member of the chaperonin containing TCP1 complex (CCT), also known as the TCP1 ring complex (TRiC). This complex consists of two identical stacked rings, each containing eight different proteins. Unfolded polypeptides enter the central cavity of the complex and are folded in an ATP-dependent manner. The complex folds various proteins, including actin and tubulin. Alternate transcriptional splice variants of this gene, encoding different isoforms, have been characterized. In addition, several pseudogenes of this gene have been located. [provided by RefSeq, Jun 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0706 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCT6A	NM_001762.4	c.*54T>A		3_prime_UTR_variant	14/14	ENST00000275603.9	NP_001753.1
CCT6A	NM_001009186.2	c.*54T>A		3_prime_UTR_variant	13/13		NP_001009186.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCT6A	ENST00000275603.9	c.*54T>A		3_prime_UTR_variant	14/14	1	NM_001762.4	ENSP00000275603	P1

Frequencies

GnomAD3 genomes AF: 0.0381 AC: 5803 AN: 152172 Hom.: 154 Cov.: 32

Gnomad AFR AF: 0.0725

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0591

Gnomad ASJ AF: 0.0268

Gnomad EAS AF: 0.0307

Gnomad SAS AF: 0.0416

Gnomad FIN AF: 0.00622

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0188

Gnomad OTH AF: 0.0426

GnomAD4 exome AF: 0.0256 AC: 27412 AN: 1068954 Hom.: 632 Cov.: 15 AF XY: 0.0258 AC XY: 14131 AN XY: 547908

Gnomad4 AFR exome AF: 0.0791

Gnomad4 AMR exome AF: 0.0979

Gnomad4 ASJ exome AF: 0.0305

Gnomad4 EAS exome AF: 0.0468

Gnomad4 SAS exome AF: 0.0412

Gnomad4 FIN exome AF: 0.00726

Gnomad4 NFE exome AF: 0.0182

Gnomad4 OTH exome AF: 0.0272

GnomAD4 genome AF: 0.0382 AC: 5819 AN: 152290 Hom.: 155 Cov.: 32 AF XY: 0.0388 AC XY: 2889 AN XY: 74466

Gnomad4 AFR AF: 0.0727

Gnomad4 AMR AF: 0.0591

Gnomad4 ASJ AF: 0.0268

Gnomad4 EAS AF: 0.0306

Gnomad4 SAS AF: 0.0417

Gnomad4 FIN AF: 0.00622

Gnomad4 NFE AF: 0.0188

Gnomad4 OTH AF: 0.0417

Alfa AF: 0.0288 Hom.: 16

Bravo AF: 0.0455

Asia WGS AF: 0.0530 AC: 182 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	3.1
DANN	Benign	0.83
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs12555; hg19: chr7-56130832; COSMIC: COSV51907353; COSMIC: COSV51907353;