2-73252734-C-T
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PP3_ModerateBS2_Supporting
The NM_006429.4(CCT7):c.1505C>T(p.Ala502Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000266 in 1,614,014 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: 𝑓 0.000039 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000025 ( 0 hom. )
Consequence
CCT7
NM_006429.4 missense
NM_006429.4 missense
Scores
6
10
3
Clinical Significance
Conservation
PhyloP100: 7.50
Genes affected
CCT7 (HGNC:1622): (chaperonin containing TCP1 subunit 7) 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. Related pseudogenes have been identified on chromosomes 5 and 6. [provided by RefSeq, Oct 2009]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PP3
MetaRNN computational evidence supports a deleterious effect, 0.888
BS2
High AC in GnomAd4 at 6 AD gene. Variant has AC lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CCT7 | ENST00000258091.10 | c.1505C>T | p.Ala502Val | missense_variant | 12/12 | 1 | NM_006429.4 | ENSP00000258091.5 | ||
CCT7 | ENST00000539919.5 | c.1373C>T | p.Ala458Val | missense_variant | 13/13 | 2 | ENSP00000437824.1 | |||
CCT7 | ENST00000540468.5 | c.1244C>T | p.Ala415Val | missense_variant | 10/10 | 2 | ENSP00000442058.1 | |||
CCT7 | ENST00000398422.2 | c.893C>T | p.Ala298Val | missense_variant | 7/7 | 2 | ENSP00000381456.2 |
Frequencies
GnomAD3 genomes AF: 0.0000394 AC: 6AN: 152170Hom.: 0 Cov.: 31
GnomAD3 genomes
AF:
AC:
6
AN:
152170
Hom.:
Cov.:
31
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.0000280 AC: 7AN: 249568Hom.: 0 AF XY: 0.0000369 AC XY: 5AN XY: 135408
GnomAD3 exomes
AF:
AC:
7
AN:
249568
Hom.:
AF XY:
AC XY:
5
AN XY:
135408
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0000253 AC: 37AN: 1461844Hom.: 0 Cov.: 31 AF XY: 0.0000289 AC XY: 21AN XY: 727218
GnomAD4 exome
AF:
AC:
37
AN:
1461844
Hom.:
Cov.:
31
AF XY:
AC XY:
21
AN XY:
727218
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome AF: 0.0000394 AC: 6AN: 152170Hom.: 0 Cov.: 31 AF XY: 0.0000269 AC XY: 2AN XY: 74316
GnomAD4 genome
AF:
AC:
6
AN:
152170
Hom.:
Cov.:
31
AF XY:
AC XY:
2
AN XY:
74316
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
ESP6500AA
AF:
AC:
0
ESP6500EA
AF:
AC:
1
ExAC
AF:
AC:
2
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 | Feb 15, 2023 | The c.1505C>T (p.A502V) alteration is located in exon 12 (coding exon 12) of the CCT7 gene. This alteration results from a C to T substitution at nucleotide position 1505, causing the alanine (A) at amino acid position 502 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Uncertain
DANN
Pathogenic
DEOGEN2
Uncertain
.;.;D;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Pathogenic
D;D;D;D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D;D;D
MetaSVM
Uncertain
D
MutationAssessor
Uncertain
.;.;M;.
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D;D;D
REVEL
Pathogenic
Sift
Benign
T;T;T;T
Sift4G
Benign
T;T;T;T
Polyphen
0.99
.;.;D;.
Vest4
MVP
MPC
1.0
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
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