rs3846599

Positions:

• chr5-10255709-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_012073.5(CCT5):​c.332-246T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.44 in 152,142 control chromosomes in the GnomAD database, including 19,228 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.44 (19228 hom., cov: 32)
• Consequence: CCT5 NM_012073.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0710

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 5-10255709-T-C is Benign according to our data. Variant chr5-10255709-T-C is described in ClinVar as [Benign]. Clinvar id is 1226164.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.638 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCT5	NM_012073.5	c.332-246T>C		intron_variant		ENST00000280326.9	NP_036205.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCT5	ENST00000280326.9	c.332-246T>C		intron_variant		1	NM_012073.5	ENSP00000280326.4

Frequencies

GnomAD3 genomes AF: 0.441 AC: 66968 AN: 152024 Hom.: 19233 Cov.: 32

Gnomad AFR AF: 0.114

Gnomad AMI AF: 0.656

Gnomad AMR AF: 0.382

Gnomad ASJ AF: 0.657

Gnomad EAS AF: 0.0577

Gnomad SAS AF: 0.325

Gnomad FIN AF: 0.650

Gnomad MID AF: 0.491

Gnomad NFE AF: 0.643

Gnomad OTH AF: 0.458

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.440 AC: 66951 AN: 152142 Hom.: 19228 Cov.: 32 AF XY: 0.434 AC XY: 32297 AN XY: 74358

Gnomad4 AFR AF: 0.113

Gnomad4 AMR AF: 0.381

Gnomad4 ASJ AF: 0.657

Gnomad4 EAS AF: 0.0576

Gnomad4 SAS AF: 0.325

Gnomad4 FIN AF: 0.650

Gnomad4 NFE AF: 0.643

Gnomad4 OTH AF: 0.456

Alfa AF: 0.595 Hom.: 59930

Bravo AF: 0.407

Asia WGS AF: 0.201 AC: 702 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 18, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.2
DANN	Benign	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

Other links and lift over

dbSNP: rs3846599; hg19: chr5-10255821;