17-34939221-C-A

Variant summary

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

The NM_006584.4(CCT6B):​c.1175G>T​(p.Arg392Ile) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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)

Consequence

CCT6B
NM_006584.4 missense

Scores

11
4
4

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.12
Variant links:
Genes affected
CCT6B (HGNC:1621): (chaperonin containing TCP1 subunit 6B) This gene encodes 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. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2015]

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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, 0.93

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CCT6BNM_006584.4 linkc.1175G>T p.Arg392Ile missense_variant 10/14 ENST00000314144.10 NP_006575.2 Q92526-1
CCT6BNM_001193529.3 linkc.1064G>T p.Arg355Ile missense_variant 9/13 NP_001180458.1 Q92526-3
CCT6BNM_001193530.2 linkc.1040G>T p.Arg347Ile missense_variant 9/13 NP_001180459.1 Q92526-2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CCT6BENST00000314144.10 linkc.1175G>T p.Arg392Ile missense_variant 10/141 NM_006584.4 ENSP00000327191.5 Q92526-1
CCT6BENST00000421975.7 linkc.1064G>T p.Arg355Ile missense_variant 9/131 ENSP00000398044.3 Q92526-3
CCT6BENST00000436961.7 linkc.1040G>T p.Arg347Ile missense_variant 9/132 ENSP00000400917.3 Q92526-2
CCT6BENST00000577307.1 linkn.2817G>T non_coding_transcript_exon_variant 4/85

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32

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 submitterclinical testingAmbry GeneticsSep 24, 2024The c.1175G>T (p.R392I) alteration is located in exon 10 (coding exon 10) of the CCT6B gene. This alteration results from a G to T substitution at nucleotide position 1175, causing the arginine (R) at amino acid position 392 to be replaced by an isoleucine (I). 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
0.68
BayesDel_addAF
Pathogenic
0.32
D
BayesDel_noAF
Pathogenic
0.22
CADD
Uncertain
26
DANN
Uncertain
0.98
DEOGEN2
Benign
0.41
.;T;.
Eigen
Pathogenic
0.79
Eigen_PC
Pathogenic
0.70
FATHMM_MKL
Uncertain
0.97
D
LIST_S2
Uncertain
0.95
D;D;D
M_CAP
Benign
0.079
D
MetaRNN
Pathogenic
0.93
D;D;D
MetaSVM
Uncertain
0.73
D
MutationAssessor
Pathogenic
3.8
.;H;.
PrimateAI
Benign
0.48
T
PROVEAN
Pathogenic
-6.3
D;D;D
REVEL
Pathogenic
0.81
Sift
Pathogenic
0.0
D;D;D
Sift4G
Pathogenic
0.0
D;D;D
Polyphen
0.97
.;D;.
Vest4
0.88
MutPred
0.65
.;Loss of MoRF binding (P = 0.0031);.;
MVP
0.87
MPC
0.31
ClinPred
1.0
D
GERP RS
4.5
Varity_R
0.88
gMVP
0.73

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.

Other links and lift over

hg19: chr17-33266240; API