NM_005998.5:c.1357C>T

Variant summary

Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1PM2

The NM_005998.5(CCT3):​c.1357C>T​(p.Gln453*) variant causes a stop gained change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: not found (cov: 32)

Consequence

CCT3
NM_005998.5 stop_gained

Scores

5
1
1

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 9.54
Variant links:
Genes affected
CCT3 (HGNC:1616): (chaperonin containing TCP1 subunit 3) 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 have been characterized for this gene. In addition, a pseudogene of this gene has been found on chromosome 8. [provided by RefSeq, Aug 2010]

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ACMG classification

Classification made for transcript

Verdict is Pathogenic. Variant got 10 ACMG points.

PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CCT3NM_005998.5 linkc.1357C>T p.Gln453* stop_gained Exon 12 of 14 ENST00000295688.8 NP_005989.3 P49368-1B3KX11Q59H77
CCT3NM_001008800.3 linkc.1243C>T p.Gln415* stop_gained Exon 10 of 12 NP_001008800.1 P49368-2B3KX11
CCT3NR_036564.2 linkn.1627C>T non_coding_transcript_exon_variant Exon 13 of 15
CCT3NR_036565.2 linkn.1578C>T non_coding_transcript_exon_variant Exon 13 of 15

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CCT3ENST00000295688.8 linkc.1357C>T p.Gln453* stop_gained Exon 12 of 14 1 NM_005998.5 ENSP00000295688.3 P49368-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
33
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
0.60
D
BayesDel_noAF
Pathogenic
0.62
CADD
Pathogenic
44
DANN
Uncertain
1.0
Eigen
Pathogenic
1.3
Eigen_PC
Pathogenic
1.1
FATHMM_MKL
Pathogenic
0.98
D
Vest4
0.90
GERP RS
5.8
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.8

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.11
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs867280074; hg19: chr1-156280785; API