chr5-10261652-C-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_012073.5(CCT5):c.1086C>G(p.Ile362Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00599 in 1,614,074 control chromosomes in the GnomAD database, including 43 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0048 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0061 ( 41 hom. )

Consequence

CCT5
NM_012073.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 1.96

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 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=0.009223521).

BP6

Variant 5-10261652-C-G is Benign according to our data. Variant chr5-10261652-C-G is described in ClinVar as [Benign]. Clinvar id is 240839.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-10261652-C-G is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population amr. GnomAdExome4 allele frequency = 0.00612 (8942/1461812) while in subpopulation AMR AF = 0.017 (759/44722). AF 95% confidence interval is 0.016. There are 41 homozygotes in GnomAdExome4. There are 4291 alleles in the male GnomAdExome4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCT5	NM_012073.5 link	c.1086C>G	p.Ile362Met	missense_variant	Exon 8 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.1086C>G	p.Ile362Met	missense_variant	Exon 8 of 11	1	NM_012073.5	ENSP00000280326.4		P48643-1

Frequencies

GnomAD3 genomes

AF:

0.00477

AC:

726

AN:

152144

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00877

Gnomad ASJ

AF:

0.000865

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00166

Gnomad FIN

AF:

0.00689

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00631

Gnomad OTH

AF:

0.00430

GnomAD2 exomes

AF:

0.00603

AC:

1517

AN:

251478

AF XY:

0.00567

show subpopulations

Gnomad AFR exome

AF:

0.000984

Gnomad AMR exome

AF:

0.0175

Gnomad ASJ exome

AF:

0.000694

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00725

Gnomad NFE exome

AF:

0.00564

Gnomad OTH exome

AF:

0.00472

GnomAD4 exome

AF:

0.00612

AC:

8942

AN:

1461812

Hom.:

Cov.:

AF XY:

0.00590

AC XY:

4291

AN XY:

727210

show subpopulations

African (AFR)

AF:

0.00102

AC:

AN:

33478

American (AMR)

AF:

0.0170

AC:

759

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.000459

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00213

AC:

184

AN:

86252

European-Finnish (FIN)

AF:

0.00822

AC:

439

AN:

53416

Middle Eastern (MID)

AF:

0.000867

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00645

AC:

7175

AN:

1111946

Other (OTH)

AF:

0.00553

AC:

334

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

441

883

1324

1766

2207

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00477

AC:

726

AN:

152262

Hom.:

Cov.:

AF XY:

0.00490

AC XY:

365

AN XY:

74458

show subpopulations

African (AFR)

AF:

0.00168

AC:

AN:

41558

American (AMR)

AF:

0.00889

AC:

136

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.000865

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00166

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00689

AC:

AN:

10600

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00629

AC:

428

AN:

68014

Other (OTH)

AF:

0.00378

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

124

166

207

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00550

Hom.:

Bravo

AF:

0.00511

TwinsUK

AF:

0.00728

AC:

ALSPAC

AF:

0.00571

AC:

ESP6500AA

AF:

0.00182

AC:

ESP6500EA

AF:

0.00663

AC:

ExAC

AF:

0.00541

AC:

657

EpiCase

AF:

0.00578

EpiControl

AF:

0.00492

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Hereditary sensory and autonomic neuropathy with spastic paraplegia

Benign:3

Jan 12, 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. -

Jan 27, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nov 29, 2023

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:3

Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Clinical Genetics, Academic Medical Center

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

May 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

CCT5: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.098

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.17

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.30

T;.;.;T;.

Eigen

Benign

-0.21

Eigen_PC

Benign

-0.043

FATHMM_MKL

Uncertain

0.93

LIST_S2

Pathogenic

0.98

D;D;D;D;D

MetaRNN

Benign

0.0092

T;T;T;T;T

MetaSVM

Benign

-0.69

MutationAssessor

Benign

1.5

L;.;.;.;.

PrimateAI

Uncertain

0.66

PROVEAN

Benign

-0.51

N;N;N;N;N

REVEL

Uncertain

0.33

Sift

Benign

0.10

T;T;T;T;T

Sift4G

Benign

0.24

T;T;T;T;T

Polyphen

0.0060

B;.;B;.;.

Vest4

0.32

MVP

0.47

MPC

0.39

ClinPred

0.014

GERP RS

3.6

Varity_R

0.25

gMVP

0.56

Mutation Taster

=84/16

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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.

chr5-10261652-C-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over