chr5-10256060-A-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_012073.5(CCT5):c.437A>T(p.Glu146Val) variant causes a missense change. The variant allele was found at a frequency of 0.0219 in 1,614,140 control chromosomes in the GnomAD database, including 469 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.017 ( 32 hom., cov: 33)

Exomes 𝑓: 0.022 ( 437 hom. )

Consequence

CCT5
NM_012073.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 6.96

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 made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.006799668).

BP6

Variant 5-10256060-A-T is Benign according to our data. Variant chr5-10256060-A-T is described in ClinVar as [Benign]. Clinvar id is 240840.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-10256060-A-T is described in Lovd as [Benign]. Variant chr5-10256060-A-T is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.017 (2585/152354) while in subpopulation SAS AF= 0.049 (237/4832). AF 95% confidence interval is 0.0439. There are 32 homozygotes in gnomad4. There are 1336 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 32 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCT5	NM_012073.5 link	c.437A>T	p.Glu146Val	missense_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.437A>T	p.Glu146Val	missense_variant	Exon 4 of 11	1	NM_012073.5	ENSP00000280326.4		P48643-1

Frequencies

GnomAD3 genomes

AF:

0.0170

AC:

2588

AN:

152236

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00374

Gnomad AMI

AF:

0.0296

Gnomad AMR

AF:

0.0139

Gnomad ASJ

AF:

0.0375

Gnomad EAS

AF:

0.00711

Gnomad SAS

AF:

0.0498

Gnomad FIN

AF:

0.0312

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.0209

Gnomad OTH

AF:

0.0134

GnomAD3 exomes

AF:

0.0228

AC:

5741

AN:

251378

Hom.:

AF XY:

0.0248

AC XY:

3372

AN XY:

135866

show subpopulations

Gnomad AFR exome

AF:

0.00277

Gnomad AMR exome

AF:

0.0141

Gnomad ASJ exome

AF:

0.0409

Gnomad EAS exome

AF:

0.00892

Gnomad SAS exome

AF:

0.0471

Gnomad FIN exome

AF:

0.0288

Gnomad NFE exome

AF:

0.0215

Gnomad OTH exome

AF:

0.0207

GnomAD4 exome

AF:

0.0224

AC:

32735

AN:

1461786

Hom.:

437

Cov.:

AF XY:

0.0233

AC XY:

16926

AN XY:

727190

show subpopulations

Gnomad4 AFR exome

AF:

0.00296

Gnomad4 AMR exome

AF:

0.0146

Gnomad4 ASJ exome

AF:

0.0404

Gnomad4 EAS exome

AF:

0.00912

Gnomad4 SAS exome

AF:

0.0467

Gnomad4 FIN exome

AF:

0.0269

Gnomad4 NFE exome

AF:

0.0212

Gnomad4 OTH exome

AF:

0.0228

GnomAD4 genome

AF:

0.0170

AC:

2585

AN:

152354

Hom.:

Cov.:

AF XY:

0.0179

AC XY:

1336

AN XY:

74502

show subpopulations

Gnomad4 AFR

AF:

0.00373

Gnomad4 AMR

AF:

0.0139

Gnomad4 ASJ

AF:

0.0375

Gnomad4 EAS

AF:

0.00713

Gnomad4 SAS

AF:

0.0490

Gnomad4 FIN

AF:

0.0312

Gnomad4 NFE

AF:

0.0209

Gnomad4 OTH

AF:

0.0142

Alfa

AF:

0.0169

Hom.:

Bravo

AF:

0.0139

TwinsUK

AF:

0.0170

AC:

ALSPAC

AF:

0.0184

AC:

ESP6500AA

AF:

0.00363

AC:

ESP6500EA

AF:

0.0224

AC:

193

ExAC

AF:

0.0239

AC:

2903

Asia WGS

AF:

0.0340

AC:

118

AN:

3478

EpiCase

AF:

0.0206

EpiControl

AF:

0.0213

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Hereditary sensory and autonomic neuropathy with spastic paraplegia

Benign:3

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 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Nov 26, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.14

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.75

D;.;.;D;.

Eigen

Uncertain

0.50

Eigen_PC

Uncertain

0.55

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.72

T;T;T;T;T

MetaRNN

Benign

0.0068

T;T;T;T;T

MetaSVM

Uncertain

0.077

MutationAssessor

Pathogenic

3.2

M;.;.;.;.

PrimateAI

Uncertain

0.51

PROVEAN

Uncertain

-2.8

D;D;D;D;D

REVEL

Uncertain

0.52

Sift

Uncertain

0.027

D;D;T;D;D

Sift4G

Uncertain

0.010

D;D;D;D;D

Polyphen

0.26

B;.;B;.;.

Vest4

0.25

MPC

0.49

ClinPred

0.031

GERP RS

5.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Varity_R

0.59

gMVP

0.64

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

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