Variant 1-156320970-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_005998.5(CCT3):c.478A>G(p.Ile160Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000547 in 1,461,852 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000055 ( 1 hom. )

Consequence

CCT3
NM_005998.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.85

Variant links:

Genes affected

CCT3 (HGNC:1616): (chaperonin containing TCP1 subunit 3) The protein encoded by this gene is 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. Alternate transcriptional splice variants have been characterized for this gene. In addition, a pseudogene of this gene has been found on chromosome 8. [provided by RefSeq, Aug 2010]

CCT3 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High AC in GnomAdExome4 at 8 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
CCT3	NM_005998.5 linkuse as main transcript	c.478A>G	p.Ile160Val	missense_variant	7/14	ENST00000295688.8	NP_005989.3
CCT3	NM_001008800.3 linkuse as main transcript	c.364A>G	p.Ile122Val	missense_variant	5/12		NP_001008800.1
CCT3	NR_036564.2 linkuse as main transcript	n.748A>G		non_coding_transcript_exon_variant	8/15
CCT3	NR_036565.2 linkuse as main transcript	n.699A>G		non_coding_transcript_exon_variant	8/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCT3	ENST00000295688.8 linkuse as main transcript	c.478A>G	p.Ile160Val	missense_variant	7/14	1	NM_005998.5	ENSP00000295688	P1	P49368-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000547

AC:

AN:

1461852

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

727222

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:

0.0000580

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000270

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000282

Hom.:

Bravo

AF:

0.0000113

ExAC

AF:

0.00000824

AC:

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

Jan 18, 2022

The c.478A>G (p.I160V) alteration is located in exon 7 (coding exon 7) of the CCT3 gene. This alteration results from a A to G substitution at nucleotide position 478, causing the isoleucine (I) at amino acid position 160 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

0.10

BayesDel_addAF

Uncertain

0.033

BayesDel_noAF

Benign

-0.19

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.36

T;.;T;T;.;T;T;.

Eigen

Benign

0.0024

Eigen_PC

Benign

0.21

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.90

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

M_CAP

Benign

0.017

MetaRNN

Uncertain

0.52

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

MetaSVM

Benign

-0.36

MutationAssessor

Benign

0.81

L;.;.;.;.;.;.;.

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Benign

0.40

PROVEAN

Benign

-0.42

N;N;N;N;N;N;N;N

REVEL

Uncertain

0.35

Sift

Benign

0.20

T;T;T;T;T;T;T;T

Sift4G

Benign

0.29

T;T;T;.;.;.;.;T

Polyphen

0.0010

B;B;.;.;.;.;.;.

Vest4

0.32

MutPred

0.76

Gain of sheet (P = 0.0344);.;.;.;.;.;.;.;

MVP

0.41

MPC

0.23

ClinPred

0.50

GERP RS

6.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.29

gMVP

0.49

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