NM_012073.5:c.426T>C

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_012073.5(CCT5):c.426T>C(p.Arg142Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.832 in 1,613,930 control chromosomes in the GnomAD database, including 565,720 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. R142R) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.75 ( 44475 hom., cov: 34)

Exomes 𝑓: 0.84 ( 521245 hom. )

Consequence

CCT5
NM_012073.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 0.0520

Publications

34 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: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.6).

BP6

Variant 5-10256049-T-C is Benign according to our data. Variant chr5-10256049-T-C is described in ClinVar as Benign. ClinVar VariationId is 350249.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.052 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.857 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCT5	NM_012073.5 link	c.426T>C	p.Arg142Arg	synonymous_variant	Exon 4 of 11	ENST00000280326.9	NP_036205.1	P48643-1V9HW37

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCT5	ENST00000280326.9 link	c.426T>C	p.Arg142Arg	synonymous_variant	Exon 4 of 11	1	NM_012073.5	ENSP00000280326.4		P48643-1

Frequencies

GnomAD3 genomes

AF:

0.746

AC:

113508

AN:

152126

Hom.:

44459

Cov.:

show subpopulations

Gnomad AFR

AF:

0.480

Gnomad AMI

AF:

0.842

Gnomad AMR

AF:

0.814

Gnomad ASJ

AF:

0.878

Gnomad EAS

AF:

0.873

Gnomad SAS

AF:

0.665

Gnomad FIN

AF:

0.859

Gnomad MID

AF:

0.803

Gnomad NFE

AF:

0.862

Gnomad OTH

AF:

0.774

GnomAD2 exomes

AF:

0.804

AC:

202101

AN:

251312

AF XY:

0.804

show subpopulations

Gnomad AFR exome

AF:

0.463

Gnomad AMR exome

AF:

0.806

Gnomad ASJ exome

AF:

0.865

Gnomad EAS exome

AF:

0.872

Gnomad FIN exome

AF:

0.858

Gnomad NFE exome

AF:

0.862

Gnomad OTH exome

AF:

0.829

GnomAD4 exome

AF:

0.841

AC:

1228930

AN:

1461686

Hom.:

521245

Cov.:

AF XY:

0.837

AC XY:

608271

AN XY:

727144

show subpopulations

African (AFR)

AF:

0.461

AC:

15427

AN:

33472

American (AMR)

AF:

0.803

AC:

35905

AN:

44712

Ashkenazi Jewish (ASJ)

AF:

0.873

AC:

22811

AN:

26134

East Asian (EAS)

AF:

0.894

AC:

35485

AN:

39698

South Asian (SAS)

AF:

0.666

AC:

57408

AN:

86244

European-Finnish (FIN)

AF:

0.863

AC:

46076

AN:

53404

Middle Eastern (MID)

AF:

0.790

AC:

4555

AN:

5764

European-Non Finnish (NFE)

AF:

0.865

AC:

961273

AN:

1111876

Other (OTH)

AF:

0.828

AC:

49990

AN:

60382

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

10891

21782

32674

43565

54456

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21156

42312

63468

84624

105780

<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:

0.746

AC:

113565

AN:

152244

Hom.:

44475

Cov.:

AF XY:

0.749

AC XY:

55743

AN XY:

74430

show subpopulations

African (AFR)

AF:

0.480

AC:

19905

AN:

41498

American (AMR)

AF:

0.813

AC:

12438

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.878

AC:

3047

AN:

3470

East Asian (EAS)

AF:

0.873

AC:

4530

AN:

5188

South Asian (SAS)

AF:

0.666

AC:

3214

AN:

4828

European-Finnish (FIN)

AF:

0.859

AC:

9109

AN:

10600

Middle Eastern (MID)

AF:

0.812

AC:

237

AN:

292

European-Non Finnish (NFE)

AF:

0.862

AC:

58678

AN:

68042

Other (OTH)

AF:

0.775

AC:

1639

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1323

2646

3970

5293

6616

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

836

1672

2508

3344

4180

<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:

0.813

Hom.:

26176

Bravo

AF:

0.735

Asia WGS

AF:

0.774

AC:

2691

AN:

3478

EpiCase

AF:

0.861

EpiControl

AF:

0.861

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Hereditary sensory and autonomic neuropathy with spastic paraplegia

Benign:4

Jul 14, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:2

Clinical Genetics, Academic Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not provided

Benign:2

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.60

CADD

Benign

(source)

DANN

Benign

0.66

PhyloP100

0.052

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Mutation Taster

=100/0

polymorphism (auto)

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over