rs118203986

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_012073.5(CCT5):c.440A>G(p.His147Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000979 in 1,614,144 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 (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H147Q) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00040 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000066 ( 0 hom. )

Consequence

CCT5
NM_012073.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts P:1U:4

Conservation

PhyloP100: 7.06

Publications

23 publications found

Variant links:

Genes affected

CCT5 (HGNC:1618): (chaperonin containing TCP1 subunit 5) 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. Mutations in this gene cause hereditary sensory and autonomic neuropathy with spastic paraplegia (HSNSP). Alternative splicing results in multiple transcript variants. Related pseudogenes have been identified on chromosomes 5 and 13. [provided by RefSeq, Apr 2015]

CCT5 Gene-Disease associations (from GenCC):

hereditary sensory and autonomic neuropathy with spastic paraplegia
Inheritance: AR, Unknown Classification: SUPPORTIVE, LIMITED Submitted by: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae)
complex neurodevelopmental disorder
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

CCT5 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.071017474).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012073.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
CCT5	NM_012073.5	MANE Select	c.440A>G	p.His147Arg	missense	Exon 4 of 11	NP_036205.1
CCT5	NM_001306153.1		c.377A>G	p.His126Arg	missense	Exon 4 of 11	NP_001293082.1
CCT5	NM_001306156.2		c.326A>G	p.His109Arg	missense	Exon 4 of 11	NP_001293085.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
CCT5	ENST00000280326.9	TSL:1 MANE Select	c.440A>G	p.His147Arg	missense	Exon 4 of 11	ENSP00000280326.4
CCT5	ENST00000503026.5	TSL:2	c.377A>G	p.His126Arg	missense	Exon 4 of 11	ENSP00000423318.1
CCT5	ENST00000515676.5	TSL:2	c.326A>G	p.His109Arg	missense	Exon 4 of 11	ENSP00000427297.1

Frequencies

GnomAD3 genomes

AF:

0.000401

AC:

AN:

152234

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00314

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:

0.0000588

Gnomad OTH

AF:

0.000956

GnomAD2 exomes

AF:

0.0000995

AC:

AN:

251374

AF XY:

0.0000736

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000578

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000352

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000664

AC:

AN:

1461792

Hom.:

Cov.:

AF XY:

0.0000674

AC XY:

AN XY:

727190

show subpopulations

African (AFR)

AF:

0.000239

AC:

AN:

33472

American (AMR)

AF:

0.000671

AC:

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26132

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86250

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53412

Middle Eastern (MID)

AF:

0.00156

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.0000279

AC:

AN:

1111956

Other (OTH)

AF:

0.000315

AC:

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.000400

AC:

AN:

152352

Hom.:

Cov.:

AF XY:

0.000349

AC XY:

AN XY:

74516

show subpopulations

African (AFR)

AF:

0.000168

AC:

AN:

41584

American (AMR)

AF:

0.00314

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000588

AC:

AN:

68032

Other (OTH)

AF:

0.000946

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000161

Hom.:

Bravo

AF:

0.000748

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ExAC

AF:

0.0000412

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.00

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Hereditary sensory and autonomic neuropathy with spastic paraplegia (3)

CCT5-related disorder (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.090

BayesDel_noAF

Uncertain

0.0

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.25

Eigen

Benign

-0.068

Eigen_PC

Benign

0.16

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.96

M_CAP

Benign

0.013

MetaRNN

Benign

0.071

MetaSVM

Benign

-0.63

MutationAssessor

Benign

0.16

PhyloP100

7.1

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-1.2

REVEL

Uncertain

0.37

Sift

Benign

0.51

Sift4G

Benign

0.35

Polyphen

0.0010

Vest4

0.76

MVP

0.69

MPC

0.40

ClinPred

0.033

GERP RS

5.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Varity_R

0.59

gMVP

0.69

Mutation Taster

=2/98

disease causing (ClinVar)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over