17-34939221-C-A
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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
NM_006584.4 missense
Scores
11
4
4
Clinical Significance
Conservation
PhyloP100: 7.12
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 |
---|---|---|---|---|---|---|---|---|
CCT6B | NM_006584.4 | c.1175G>T | p.Arg392Ile | missense_variant | 10/14 | ENST00000314144.10 | NP_006575.2 | |
CCT6B | NM_001193529.3 | c.1064G>T | p.Arg355Ile | missense_variant | 9/13 | NP_001180458.1 | ||
CCT6B | NM_001193530.2 | c.1040G>T | p.Arg347Ile | missense_variant | 9/13 | NP_001180459.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CCT6B | ENST00000314144.10 | c.1175G>T | p.Arg392Ile | missense_variant | 10/14 | 1 | NM_006584.4 | ENSP00000327191.5 | ||
CCT6B | ENST00000421975.7 | c.1064G>T | p.Arg355Ile | missense_variant | 9/13 | 1 | ENSP00000398044.3 | |||
CCT6B | ENST00000436961.7 | c.1040G>T | p.Arg347Ile | missense_variant | 9/13 | 2 | ENSP00000400917.3 | |||
CCT6B | ENST00000577307.1 | n.2817G>T | non_coding_transcript_exon_variant | 4/8 | 5 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
GnomAD4 genome Cov.: 32
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 submitter | clinical testing | Ambry Genetics | Sep 24, 2024 | The 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:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
.;T;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D
M_CAP
Benign
D
MetaRNN
Pathogenic
D;D;D
MetaSVM
Uncertain
D
MutationAssessor
Pathogenic
.;H;.
PrimateAI
Benign
T
PROVEAN
Pathogenic
D;D;D
REVEL
Pathogenic
Sift
Pathogenic
D;D;D
Sift4G
Pathogenic
D;D;D
Polyphen
0.97
.;D;.
Vest4
MutPred
0.65
.;Loss of MoRF binding (P = 0.0031);.;
MVP
MPC
0.31
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.