21-29061362-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_006585.4(CCT8):​c.1340C>T​(p.Ala447Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000372 in 1,613,892 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

CCT8
NM_006585.4 missense

Scores

3
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.08
Variant links:
Genes affected
CCT8 (HGNC:1623): (chaperonin containing TCP1 subunit 8) This gene encodes the theta subunit of the CCT chaperonin, which is abundant in the eukaryotic cytosol and may be involved in the transport and assembly of newly synthesized proteins. Alternative splicing results in multiple transcript variants of this gene. A pseudogene related to this gene is located on chromosome 1. [provided by RefSeq, Sep 2013]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.15089688).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CCT8NM_006585.4 linkuse as main transcriptc.1340C>T p.Ala447Val missense_variant 13/15 ENST00000286788.9 NP_006576.2 P50990-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CCT8ENST00000286788.9 linkuse as main transcriptc.1340C>T p.Ala447Val missense_variant 13/151 NM_006585.4 ENSP00000286788.4 P50990-1

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152156
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000796
AC:
2
AN:
251292
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135820
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000289
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.00000342
AC:
5
AN:
1461736
Hom.:
0
Cov.:
32
AF XY:
0.00000138
AC XY:
1
AN XY:
727178
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.0000447
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:
0.00
Gnomad4 OTH exome
AF:
0.0000331
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152156
Hom.:
0
Cov.:
32
AF XY:
0.0000134
AC XY:
1
AN XY:
74350
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000655
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000434
Hom.:
0
Bravo
AF:
0.0000604
ExAC
AF:
0.00000824
AC:
1

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 GeneticsJan 09, 2024The c.1340C>T (p.A447V) alteration is located in exon 13 (coding exon 13) of the CCT8 gene. This alteration results from a C to T substitution at nucleotide position 1340, causing the alanine (A) at amino acid position 447 to be replaced by a valine (V). 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
Benign
0.081
BayesDel_addAF
Benign
-0.18
T
BayesDel_noAF
Benign
-0.32
CADD
Benign
17
DANN
Benign
0.84
DEOGEN2
Benign
0.19
.;T;.
Eigen
Benign
-0.65
Eigen_PC
Benign
-0.36
FATHMM_MKL
Uncertain
0.93
D
LIST_S2
Uncertain
0.90
D;D;D
M_CAP
Benign
0.015
T
MetaRNN
Benign
0.15
T;T;T
MetaSVM
Benign
-0.85
T
MutationAssessor
Benign
-0.23
.;N;.
PrimateAI
Uncertain
0.73
T
PROVEAN
Benign
-0.15
N;N;.
REVEL
Benign
0.29
Sift
Benign
1.0
T;T;.
Sift4G
Benign
1.0
T;T;T
Polyphen
0.0040
.;B;.
Vest4
0.31
MutPred
0.41
.;Loss of helix (P = 0.2022);.;
MVP
0.33
MPC
0.16
ClinPred
0.12
T
GERP RS
4.6
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.14
gMVP
0.55

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

LitVar

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

Other links and lift over

dbSNP: rs763381759; hg19: chr21-30433683; API