5-10256049-T-C

Position:

chr5-10256049-T-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_012073.5(CCT5):c.426T>C(p.Arg142=) 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 (★★).

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

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 -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 id is 350249.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-10256049-T-C is described in Lovd as [Benign].

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/exons	MANE	Protein	UniProt
CCT5	NM_012073.5 linkuse as main transcript	c.426T>C	p.Arg142=	synonymous_variant	4/11	ENST00000280326.9	NP_036205.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCT5	ENST00000280326.9 linkuse as main transcript	c.426T>C	p.Arg142=	synonymous_variant	4/11	1	NM_012073.5	ENSP00000280326	P1	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

GnomAD3 exomes

AF:

0.804

AC:

202101

AN:

251312

Hom.:

82855

AF XY:

0.804

AC XY:

109248

AN XY:

135840

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 SAS exome

AF:

0.666

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

Gnomad4 AFR exome

AF:

0.461

Gnomad4 AMR exome

AF:

0.803

Gnomad4 ASJ exome

AF:

0.873

Gnomad4 EAS exome

AF:

0.894

Gnomad4 SAS exome

AF:

0.666

Gnomad4 FIN exome

AF:

0.863

Gnomad4 NFE exome

AF:

0.865

Gnomad4 OTH exome

AF:

0.828

GnomAD4 genome

AF:

0.746

AC:

113565

AN:

152244

Hom.:

44475

Cov.:

AF XY:

0.749

AC XY:

55743

AN XY:

74430

show subpopulations

Gnomad4 AFR

AF:

0.480

Gnomad4 AMR

AF:

0.813

Gnomad4 ASJ

AF:

0.878

Gnomad4 EAS

AF:

0.873

Gnomad4 SAS

AF:

0.666

Gnomad4 FIN

AF:

0.859

Gnomad4 NFE

AF:

0.862

Gnomad4 OTH

AF:

0.775

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

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 14, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	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. -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

not specified

Benign:2

Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.60

CADD

Benign

DANN

Benign

0.66

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

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