21-29061555-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

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

Publications

7 publications found

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 Gene-Disease associations (from GenCC):

complex neurodevelopmental disorder
Inheritance: AD Classification: LIMITED Submitted by: G2P
neurodevelopmental disorder
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

CCT8 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006585.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CCT8	NM_006585.4	MANE Select	c.1225G>A	p.Val409Ile	missense	Exon 12 of 15	NP_006576.2
CCT8	NM_001282907.2		c.1168G>A	p.Val390Ile	missense	Exon 13 of 16	NP_001269836.1	P50990-2
CCT8	NM_001282908.2		c.1072G>A	p.Val358Ile	missense	Exon 12 of 15	NP_001269837.1	Q7Z759

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CCT8	ENST00000286788.9	TSL:1 MANE Select	c.1225G>A	p.Val409Ile	missense	Exon 12 of 15	ENSP00000286788.4	P50990-1
CCT8	ENST00000470450.5	TSL:1	n.1299G>A		non_coding_transcript_exon	Exon 12 of 15
CCT8	ENST00000936253.1		c.1219G>A	p.Val407Ile	missense	Exon 12 of 15	ENSP00000606312.1

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

GnomAD2 exomes

AF:

0.00551

AC:

1385

AN:

251374

AF XY:

0.00400

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 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

African (AFR)

AF:

0.0733

AC:

2450

AN:

33438

American (AMR)

AF:

0.00378

AC:

169

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0000383

AC:

AN:

26124

East Asian (EAS)

AF:

0.00

AC:

AN:

39694

South Asian (SAS)

AF:

0.000174

AC:

AN:

86238

European-Finnish (FIN)

AF:

0.0000187

AC:

AN:

53394

Middle Eastern (MID)

AF:

0.00486

AC:

AN:

5756

European-Non Finnish (NFE)

AF:

0.000240

AC:

267

AN:

1111482

Other (OTH)

AF:

0.00469

AC:

283

AN:

60370

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.452

Heterozygous variant carriers

139

279

418

558

697

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

164

246

328

410

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0209

AC:

3177

AN:

152038

Hom.:

115

Cov.:

AF XY:

0.0201

AC XY:

1492

AN XY:

74324

show subpopulations

African (AFR)

AF:

0.0722

AC:

2995

AN:

41472

American (AMR)

AF:

0.00793

AC:

121

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.000208

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10568

Middle Eastern (MID)

AF:

0.0170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000265

AC:

AN:

67954

Other (OTH)

AF:

0.0176

AC:

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

152

303

455

606

758

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

108

144

180

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00497

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

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.28

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.28

Eigen

Benign

0.017

Eigen_PC

Benign

0.13

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.95

MetaRNN

Benign

0.0058

MetaSVM

Benign

-0.59

MutationAssessor

Benign

1.7

PhyloP100

3.0

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-0.28

REVEL

Benign

0.24

Sift

Benign

0.096

Sift4G

Benign

0.14

Polyphen

0.010

Vest4

0.23

MVP

0.52

MPC

0.21

ClinPred

0.012

GERP RS

4.3

PromoterAI

-0.011

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.15

gMVP

0.34

Mutation Taster

=97/3

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over