Variant chr7-56058028-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_001762.4(CCT6A):c.650G>A(p.Arg217Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,460,418 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

CCT6A
NM_001762.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.10

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.923

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCT6A	NM_001762.4 linkuse as main transcript	c.650G>A	p.Arg217Gln	missense_variant	6/14	ENST00000275603.9
CCT6A	NM_001009186.2 linkuse as main transcript	c.515G>A	p.Arg172Gln	missense_variant	5/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCT6A	ENST00000275603.9 linkuse as main transcript	c.650G>A	p.Arg217Gln	missense_variant	6/14	1	NM_001762.4	P1	P40227-1
CCT6A	ENST00000335503.3 linkuse as main transcript	c.515G>A	p.Arg172Gln	missense_variant	5/13	5			P40227-2
CCT6A	ENST00000482776.1 linkuse as main transcript	n.139G>A		non_coding_transcript_exon_variant	2/4	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1460418

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726642

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 28, 2021

The c.650G>A (p.R217Q) alteration is located in exon 6 (coding exon 6) of the CCT6A gene. This alteration results from a G to A substitution at nucleotide position 650, causing the arginine (R) at amino acid position 217 to be replaced by a glutamine (Q). 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

Pathogenic

0.98

BayesDel_addAF

Pathogenic

0.27

BayesDel_noAF

Pathogenic

0.15

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.65

D;.

Eigen

Pathogenic

0.99

Eigen_PC

Pathogenic

0.92

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.91

D;D

M_CAP

Uncertain

0.24

MetaRNN

Pathogenic

0.92

D;D

MetaSVM

Uncertain

0.71

MutationAssessor

Pathogenic

3.4

M;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.70

PROVEAN

Uncertain

-3.6

D;D

REVEL

Pathogenic

0.76

Sift

Pathogenic

0.0

D;D

Sift4G

Uncertain

0.012

D;D

Polyphen

1.0

D;.

Vest4

0.88

MutPred

0.66

Gain of ubiquitination at K222 (P = 0.1047);.;

MVP

0.80

MPC

0.57

ClinPred

1.0

GERP RS

5.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.85

gMVP

0.31

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over