chr5-10264850-A-G

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.*67A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.825 in 1,591,202 control chromosomes in the GnomAD database, including 549,137 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.74 ( 43755 hom., cov: 32)

Exomes 𝑓: 0.83 ( 505382 hom. )

Consequence

CCT5
NM_012073.5 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.0910

Publications

17 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:

ENSG00000271980 (HGNC:58210):

ENSG00000271980 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=-0.81).

BP6

Variant 5-10264850-A-G is Benign according to our data. Variant chr5-10264850-A-G is described in ClinVar as Benign. ClinVar VariationId is 350262.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.85 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCT5	NM_012073.5 link	c.*67A>G		3_prime_UTR_variant	Exon 11 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.*67A>G		3_prime_UTR_variant	Exon 11 of 11	1	NM_012073.5	ENSP00000280326.4		P48643-1

Frequencies

GnomAD3 genomes

AF:

0.739

AC:

112372

AN:

152050

Hom.:

43738

Cov.:

show subpopulations

Gnomad AFR

AF:

0.466

Gnomad AMI

AF:

0.874

Gnomad AMR

AF:

0.809

Gnomad ASJ

AF:

0.877

Gnomad EAS

AF:

0.866

Gnomad SAS

AF:

0.664

Gnomad FIN

AF:

0.859

Gnomad MID

AF:

0.804

Gnomad NFE

AF:

0.856

Gnomad OTH

AF:

0.767

GnomAD4 exome

AF:

0.834

AC:

1200497

AN:

1439034

Hom.:

505382

Cov.:

AF XY:

0.830

AC XY:

595408

AN XY:

717164

show subpopulations

African (AFR)

AF:

0.448

AC:

14793

AN:

33032

American (AMR)

AF:

0.801

AC:

35620

AN:

44472

Ashkenazi Jewish (ASJ)

AF:

0.872

AC:

22573

AN:

25884

East Asian (EAS)

AF:

0.890

AC:

35070

AN:

39414

South Asian (SAS)

AF:

0.664

AC:

56622

AN:

85240

European-Finnish (FIN)

AF:

0.862

AC:

45700

AN:

53016

Middle Eastern (MID)

AF:

0.790

AC:

4388

AN:

5554

European-Non Finnish (NFE)

AF:

0.857

AC:

936715

AN:

1092846

Other (OTH)

AF:

0.823

AC:

49016

AN:

59576

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

8882

17764

26645

35527

44409

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20666

41332

61998

82664

103330

<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:

0.739

AC:

112429

AN:

152168

Hom.:

43755

Cov.:

AF XY:

0.742

AC XY:

55212

AN XY:

74396

show subpopulations

African (AFR)

AF:

0.466

AC:

19342

AN:

41490

American (AMR)

AF:

0.809

AC:

12368

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.877

AC:

3045

AN:

3472

East Asian (EAS)

AF:

0.866

AC:

4485

AN:

5178

South Asian (SAS)

AF:

0.664

AC:

3203

AN:

4822

European-Finnish (FIN)

AF:

0.859

AC:

9096

AN:

10590

Middle Eastern (MID)

AF:

0.813

AC:

239

AN:

294

European-Non Finnish (NFE)

AF:

0.856

AC:

58231

AN:

68008

Other (OTH)

AF:

0.768

AC:

1623

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1294

2588

3883

5177

6471

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

830

1660

2490

3320

4150

<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:

0.799

Hom.:

11093

Bravo

AF:

0.728

Asia WGS

AF:

0.773

AC:

2684

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Hereditary sensory and autonomic neuropathy with spastic paraplegia

Benign:2

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. -

Jul 14, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Jun 18, 2021

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

-0.81

CADD

Benign

0.055

(source)

DANN

Benign

0.66

PhyloP100

-0.091

RBP_binding_hub_radar

0.97

RBP_regulation_power_radar

2.1

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