2-73252746-C-T
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_006429.4(CCT7):c.1517C>T(p.Ala506Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000031 in 1,614,136 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000020 ( 1 hom., cov: 31)
Exomes 𝑓: 0.0000014 ( 0 hom. )
Consequence
CCT7
NM_006429.4 missense
NM_006429.4 missense
Scores
13
3
1
Clinical Significance
Conservation
PhyloP100: 7.47
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.982
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CCT7 | NM_006429.4 | c.1517C>T | p.Ala506Val | missense_variant | 12/12 | ENST00000258091.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CCT7 | ENST00000258091.10 | c.1517C>T | p.Ala506Val | missense_variant | 12/12 | 1 | NM_006429.4 | P1 | |
CCT7 | ENST00000539919.5 | c.1385C>T | p.Ala462Val | missense_variant | 13/13 | 2 | |||
CCT7 | ENST00000540468.5 | c.1256C>T | p.Ala419Val | missense_variant | 10/10 | 2 | |||
CCT7 | ENST00000398422.2 | c.905C>T | p.Ala302Val | missense_variant | 7/7 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152148Hom.: 1 Cov.: 31
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GnomAD3 exomes AF: 0.00000401 AC: 1AN: 249564Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135408
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GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461870Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 727240
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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 | Dec 16, 2021 | The c.1517C>T (p.A506V) 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 1517, causing the alanine (A) at amino acid position 506 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
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Benign
Dann
Pathogenic
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Pathogenic
D;D;D;D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D;D;D
MetaSVM
Pathogenic
D
MutationTaster
Benign
D;D;D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D;D;D
REVEL
Uncertain
Sift
Pathogenic
D;D;D;D
Sift4G
Pathogenic
D;D;D;D
Polyphen
1.0
.;.;D;.
Vest4
MutPred
0.94
.;.;Gain of glycosylation at T504 (P = 0.337);.;
MVP
MPC
1.3
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at