Variant 21-29061555-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_006585.4(CCT8):c.1225G>A(p.Val409Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00396 in 1,613,258 control chromosomes in the GnomAD database, including 207 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.021 ( 115 hom., cov: 32)

Exomes 𝑓: 0.0022 ( 92 hom. )

Consequence

CCT8
NM_006585.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 3.03

Variant links:

Genes affected

CCT8 (HGNC:1623): (chaperonin containing TCP1 subunit 8) This gene encodes the theta subunit of the CCT chaperonin, which is abundant in the eukaryotic cytosol and may be involved in the transport and assembly of newly synthesized proteins. Alternative splicing results in multiple transcript variants of this gene. A pseudogene related to this gene is located on chromosome 1. [provided by RefSeq, Sep 2013]

CCT8 links:

CCT8 (HGNC:):

CCT8 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005824864).

BP6

Variant 21-29061555-C-T is Benign according to our data. Variant chr21-29061555-C-T is described in ClinVar as [Benign]. Clinvar id is 769121.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0701 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCT8	NM_006585.4 linkuse as main transcript	c.1225G>A	p.Val409Ile	missense_variant	12/15	ENST00000286788.9	NP_006576.2	P50990-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCT8	ENST00000286788.9 linkuse as main transcript	c.1225G>A	p.Val409Ile	missense_variant	12/15	1	NM_006585.4	ENSP00000286788.4		P50990-1

Frequencies

GnomAD3 genomes

AF:

0.0208

AC:

3167

AN:

151918

Hom.:

115

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0722

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00794

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.000265

Gnomad OTH

AF:

0.0178

GnomAD3 exomes

AF:

0.00551

AC:

1385

AN:

251374

Hom.:

AF XY:

0.00400

AC XY:

543

AN XY:

135862

show subpopulations

Gnomad AFR exome

AF:

0.0740

Gnomad AMR exome

AF:

0.00330

Gnomad ASJ exome

AF:

0.0000992

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.000163

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000405

Gnomad OTH exome

AF:

0.00261

GnomAD4 exome

AF:

0.00220

AC:

3214

AN:

1461220

Hom.:

Cov.:

AF XY:

0.00197

AC XY:

1433

AN XY:

726956

show subpopulations

Gnomad4 AFR exome

AF:

0.0733

Gnomad4 AMR exome

AF:

0.00378

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000174

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000240

Gnomad4 OTH exome

AF:

0.00469

GnomAD4 genome

AF:

0.0209

AC:

3177

AN:

152038

Hom.:

115

Cov.:

AF XY:

0.0201

AC XY:

1492

AN XY:

74324

show subpopulations

Gnomad4 AFR

AF:

0.0722

Gnomad4 AMR

AF:

0.00793

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000265

Gnomad4 OTH

AF:

0.0176

Alfa

AF:

0.00420

Hom.:

Bravo

AF:

0.0239

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.0785

AC:

346

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.00695

AC:

844

Asia WGS

AF:

0.00289

AC:

AN:

3478

EpiCase

AF:

0.000436

EpiControl

AF:

0.000771

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	May 18, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.28

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.28

.;T;.

Eigen

Benign

0.017

Eigen_PC

Benign

0.13

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.95

D;D;D

MetaRNN

Benign

0.0058

T;T;T

MetaSVM

Benign

-0.59

MutationAssessor

Benign

1.7

.;L;.

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-0.28

N;N;.

REVEL

Benign

0.24

Sift

Benign

0.096

T;T;.

Sift4G

Benign

0.14

T;T;T

Polyphen

0.010

.;B;.

Vest4

0.23

MVP

0.52

MPC

0.21

ClinPred

0.012

GERP RS

4.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.15

gMVP

0.34

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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