2-73252769-G-A
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_006429.4(CCT7):c.1540G>A(p.Val514Met) variant causes a missense change. The variant allele was found at a frequency of 0.0000353 in 1,614,158 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000079 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000031 ( 1 hom. )
Consequence
CCT7
NM_006429.4 missense
NM_006429.4 missense
Scores
9
8
Clinical Significance
Conservation
PhyloP100: 4.67
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_benign. Variant got -6 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.0900445).
BS2
?
High AC in GnomAd at 12 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CCT7 | NM_006429.4 | c.1540G>A | p.Val514Met | missense_variant | 12/12 | ENST00000258091.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CCT7 | ENST00000258091.10 | c.1540G>A | p.Val514Met | missense_variant | 12/12 | 1 | NM_006429.4 | P1 | |
CCT7 | ENST00000539919.5 | c.1408G>A | p.Val470Met | missense_variant | 13/13 | 2 | |||
CCT7 | ENST00000540468.5 | c.1279G>A | p.Val427Met | missense_variant | 10/10 | 2 | |||
CCT7 | ENST00000398422.2 | c.928G>A | p.Val310Met | missense_variant | 7/7 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000789 AC: 12AN: 152156Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.000148 AC: 37AN: 249560Hom.: 0 AF XY: 0.000126 AC XY: 17AN XY: 135408
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GnomAD4 exome AF: 0.0000308 AC: 45AN: 1461884Hom.: 1 Cov.: 31 AF XY: 0.0000289 AC XY: 21AN XY: 727242
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GnomAD4 genome ? AF: 0.0000788 AC: 12AN: 152274Hom.: 0 Cov.: 31 AF XY: 0.0000806 AC XY: 6AN XY: 74460
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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 | Nov 08, 2022 | The c.1540G>A (p.V514M) alteration is located in exon 12 (coding exon 12) of the CCT7 gene. This alteration results from a G to A substitution at nucleotide position 1540, causing the valine (V) at amino acid position 514 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D;D
M_CAP
Benign
D
MetaRNN
Benign
T;T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N;N
REVEL
Uncertain
Sift
Uncertain
D;D;D;D
Sift4G
Uncertain
D;D;D;D
Polyphen
0.95
.;.;P;.
Vest4
MVP
MPC
0.55
ClinPred
T
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