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GeneBe

2-73252679-A-G

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_006429.4(CCT7):c.1450A>G(p.Ile484Val) variant causes a missense change. The variant allele was found at a frequency of 0.0001 in 1,614,018 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 31)
Exomes 𝑓: 0.00011 ( 0 hom. )

Consequence

CCT7
NM_006429.4 missense

Scores

1
4
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.03
Variant links:
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 Likely_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.1699386).
BS2
High AC in GnomAd at 8 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CCT7NM_006429.4 linkuse as main transcriptc.1450A>G p.Ile484Val missense_variant 12/12 ENST00000258091.10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CCT7ENST00000258091.10 linkuse as main transcriptc.1450A>G p.Ile484Val missense_variant 12/121 NM_006429.4 P1Q99832-1
CCT7ENST00000539919.5 linkuse as main transcriptc.1318A>G p.Ile440Val missense_variant 13/132 Q99832-3
CCT7ENST00000540468.5 linkuse as main transcriptc.1189A>G p.Ile397Val missense_variant 10/102 Q99832-4
CCT7ENST00000398422.2 linkuse as main transcriptc.838A>G p.Ile280Val missense_variant 7/72 Q99832-2

Frequencies

GnomAD3 genomes
AF:
0.0000526
AC:
8
AN:
152178
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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:
0.000103
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000841
AC:
21
AN:
249580
Hom.:
0
AF XY:
0.0000886
AC XY:
12
AN XY:
135408
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
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:
0.000185
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000105
AC:
154
AN:
1461840
Hom.:
0
Cov.:
31
AF XY:
0.000106
AC XY:
77
AN XY:
727218
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
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:
0.000136
Gnomad4 OTH exome
AF:
0.0000497
GnomAD4 genome
AF:
0.0000526
AC:
8
AN:
152178
Hom.:
0
Cov.:
31
AF XY:
0.0000135
AC XY:
1
AN XY:
74336
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000103
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000116
Hom.:
0
Bravo
AF:
0.0000793
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000357
AC:
3
ExAC
AF:
0.000140
AC:
17
EpiCase
AF:
0.0000545
EpiControl
AF:
0.0000593

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 30, 2024The c.1450A>G (p.I484V) alteration is located in exon 12 (coding exon 12) of the CCT7 gene. This alteration results from a A to G substitution at nucleotide position 1450, causing the isoleucine (I) at amino acid position 484 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
0.060
BayesDel_addAF
Benign
-0.16
T
BayesDel_noAF
Benign
-0.19
Cadd
Benign
19
Dann
Uncertain
0.98
Eigen
Benign
-0.12
Eigen_PC
Benign
0.10
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Uncertain
0.96
D;D;D;D
M_CAP
Benign
0.037
D
MetaRNN
Benign
0.17
T;T;T;T
MetaSVM
Benign
-0.76
T
MutationTaster
Benign
1.0
D;D;D;D;D;D;D
PrimateAI
Uncertain
0.49
T
PROVEAN
Benign
-0.13
N;N;N;N
REVEL
Uncertain
0.30
Sift
Benign
0.76
T;T;T;T
Sift4G
Benign
0.70
T;T;T;T
Polyphen
0.014
.;.;B;.
Vest4
0.50
MVP
0.16
MPC
0.38
ClinPred
0.14
T
GERP RS
5.0
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.20
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: rs371881724; hg19: chr2-73479807; API