Variant 2-73250331-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP4

The NM_006429.4(CCT7):c.1096A>G(p.Lys366Glu) variant causes a missense change. The variant allele was found at a frequency of 0.00000434 in 1,613,998 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

CCT7
NM_006429.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.06

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]

CCT7 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -1 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.3217918).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCT7	NM_006429.4 linkuse as main transcript	c.1096A>G	p.Lys366Glu	missense_variant	10/12	ENST00000258091.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCT7	ENST00000258091.10 linkuse as main transcript	c.1096A>G	p.Lys366Glu	missense_variant	10/12	1	NM_006429.4	P1	Q99832-1
CCT7	ENST00000539919.5 linkuse as main transcript	c.964A>G	p.Lys322Glu	missense_variant	11/13	2			Q99832-3
CCT7	ENST00000540468.5 linkuse as main transcript	c.835A>G	p.Lys279Glu	missense_variant	8/10	2			Q99832-4
CCT7	ENST00000398422.2 linkuse as main transcript	c.484A>G	p.Lys162Glu	missense_variant	5/7	2			Q99832-2

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152116

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000401

AC:

AN:

249570

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135404

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000290

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:

0.00

GnomAD4 exome

AF:

0.00000410

AC:

AN:

1461882

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.0000224

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:

0.00000360

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152116

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74322

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

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

Oct 20, 2023

The c.1096A>G (p.K366E) alteration is located in exon 10 (coding exon 10) of the CCT7 gene. This alteration results from a A to G substitution at nucleotide position 1096, causing the lysine (K) at amino acid position 366 to be replaced by a glutamic acid (E). 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

0.10

BayesDel_addAF

Benign

0.0051

BayesDel_noAF

Benign

-0.15

Cadd

Uncertain

Dann

Uncertain

0.99

Eigen

Benign

0.047

Eigen_PC

Benign

0.20

FATHMM_MKL

Uncertain

0.96

LIST_S2

Pathogenic

0.97

D;D;D;D

M_CAP

Benign

0.049

MetaRNN

Benign

0.32

T;T;T;T

MetaSVM

Benign

-0.43

MutationTaster

Benign

1.0

D;D;D;D;D;D;D

PrimateAI

Pathogenic

0.80

PROVEAN

Benign

-0.68

N;N;N;N

REVEL

Uncertain

0.37

Sift

Benign

0.37

T;T;T;T

Sift4G

Benign

0.46

T;T;T;T

Polyphen

0.0010

.;.;B;.

Vest4

0.59

MutPred

0.40

.;.;Gain of ubiquitination at K368 (P = 0.0325);.;

MVP

0.48

MPC

0.65

ClinPred

0.53

GERP RS

4.6

RBP_binding_hub_radar

0.97

RBP_regulation_power_radar

2.8

Varity_R

0.45

gMVP

0.80

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over