rs12555

Variant names:

• chr7-56063139-T-A
• rs12555
• NM_001762.4:c.*54T>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001762.4(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 NM_001762.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.03
• Publications: 7 publications found

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]

CCT6A Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: MODERATE Submitted by: G2P
• neurodevelopmental disorder

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
CCT6A	NM_001762.4	c.*54T>A		3_prime_UTR_variant	Exon 14 of 14	ENST00000275603.9	NP_001753.1
CCT6A	NM_001009186.2	c.*54T>A		3_prime_UTR_variant	Exon 13 of 13		NP_001009186.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCT6A	ENST00000275603.9	c.*54T>A		3_prime_UTR_variant	Exon 14 of 14	1	NM_001762.4	ENSP00000275603.4

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

African (AFR) AF: 0.0791 AC: 2023 AN: 25584

American (AMR) AF: 0.0979 AC: 4180 AN: 42678

Ashkenazi Jewish (ASJ) AF: 0.0305 AC: 715 AN: 23480

East Asian (EAS) AF: 0.0468 AC: 1767 AN: 37786

South Asian (SAS) AF: 0.0412 AC: 3179 AN: 77124

European-Finnish (FIN) AF: 0.00726 AC: 385 AN: 53006

Middle Eastern (MID) AF: 0.0266 AC: 133 AN: 5002

European-Non Finnish (NFE) AF: 0.0182 AC: 13739 AN: 756858

Other (OTH) AF: 0.0272 AC: 1291 AN: 47436

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

African (AFR) AF: 0.0727 AC: 3022 AN: 41560

American (AMR) AF: 0.0591 AC: 904 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0268 AC: 93 AN: 3470

East Asian (EAS) AF: 0.0306 AC: 159 AN: 5192

South Asian (SAS) AF: 0.0417 AC: 201 AN: 4822

European-Finnish (FIN) AF: 0.00622 AC: 66 AN: 10612

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0188 AC: 1276 AN: 68028

Other (OTH) AF: 0.0417 AC: 88 AN: 2110

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
PhyloP100		-1.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

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