chr5-10250331-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_012073.5(CCT5):c.-10T>C variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.825 in 1,613,744 control chromosomes in the GnomAD database, including 556,134 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.74 ( 43685 hom., cov: 33)

Exomes 𝑓: 0.83 ( 512449 hom. )

Consequence

CCT5
NM_012073.5 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.25

Publications

27 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 5-10250331-T-C is Benign according to our data. Variant chr5-10250331-T-C is described in ClinVar as [Benign]. Clinvar id is 350246.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.849 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCT5	NM_012073.5 link	c.-10T>C		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 11	ENST00000280326.9	NP_036205.1	P48643-1V9HW37
CCT5	NM_012073.5 link	c.-10T>C		5_prime_UTR_variant	Exon 1 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.-10T>C		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 11	1	NM_012073.5	ENSP00000280326.4		P48643-1
CCT5	ENST00000280326.9 link	c.-10T>C		5_prime_UTR_variant	Exon 1 of 11	1	NM_012073.5	ENSP00000280326.4		P48643-1

Frequencies

GnomAD3 genomes

AF:

0.738

AC:

112307

AN:

152078

Hom.:

43668

Cov.:

show subpopulations

Gnomad AFR

AF:

0.466

Gnomad AMI

AF:

0.838

Gnomad AMR

AF:

0.808

Gnomad ASJ

AF:

0.880

Gnomad EAS

AF:

0.865

Gnomad SAS

AF:

0.666

Gnomad FIN

AF:

0.859

Gnomad MID

AF:

0.807

Gnomad NFE

AF:

0.855

Gnomad OTH

AF:

0.766

GnomAD2 exomes

AF:

0.799

AC:

200340

AN:

250774

AF XY:

0.799

show subpopulations

Gnomad AFR exome

AF:

0.449

Gnomad AMR exome

AF:

0.803

Gnomad ASJ exome

AF:

0.868

Gnomad EAS exome

AF:

0.863

Gnomad FIN exome

AF:

0.857

Gnomad NFE exome

AF:

0.855

Gnomad OTH exome

AF:

0.826

GnomAD4 exome

AF:

0.834

AC:

1218449

AN:

1461548

Hom.:

512449

Cov.:

AF XY:

0.830

AC XY:

603262

AN XY:

727076

show subpopulations

African (AFR)

AF:

0.448

AC:

15005

AN:

33474

American (AMR)

AF:

0.800

AC:

35777

AN:

44704

Ashkenazi Jewish (ASJ)

AF:

0.875

AC:

22867

AN:

26134

East Asian (EAS)

AF:

0.890

AC:

35326

AN:

39696

South Asian (SAS)

AF:

0.665

AC:

57323

AN:

86240

European-Finnish (FIN)

AF:

0.862

AC:

45870

AN:

53228

Middle Eastern (MID)

AF:

0.788

AC:

4548

AN:

5768

European-Non Finnish (NFE)

AF:

0.856

AC:

952077

AN:

1111916

Other (OTH)

AF:

0.822

AC:

49656

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

11314

22628

33941

45255

56569

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.738

AC:

112366

AN:

152196

Hom.:

43685

Cov.:

AF XY:

0.742

AC XY:

55180

AN XY:

74408

show subpopulations

African (AFR)

AF:

0.467

AC:

19358

AN:

41490

American (AMR)

AF:

0.808

AC:

12359

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.880

AC:

3055

AN:

3472

East Asian (EAS)

AF:

0.865

AC:

4469

AN:

5166

South Asian (SAS)

AF:

0.667

AC:

3209

AN:

4814

European-Finnish (FIN)

AF:

0.859

AC:

9104

AN:

10602

Middle Eastern (MID)

AF:

0.816

AC:

240

AN:

294

European-Non Finnish (NFE)

AF:

0.855

AC:

58183

AN:

68032

Other (OTH)

AF:

0.768

AC:

1625

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1333

2666

3999

5332

6665

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.818

Hom.:

55671

Bravo

AF:

0.727

Asia WGS

AF:

0.773

AC:

2687

AN:

3478

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

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Jul 14, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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. -

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

- -

not specified

Benign:1

Clinical Genetics, Academic Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

7.0

(source)

DANN

Benign

0.63

PhyloP100

-2.3

PromoterAI

-0.083

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Mutation Taster

=297/3

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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chr5-10250331-T-C

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