rs3846599

Variant names:

• chr5-10255709-T-C
• rs3846599
• NM_012073.5:c.332-246T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 publications found

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

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012073.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCT5	NM_012073.5	MANE Select	c.332-246T>C		intron	N/A	NP_036205.1	P48643-1
	CCT5	NM_001306153.1		c.269-246T>C		intron	N/A	NP_001293082.1	B4DX08
	CCT5	NM_001306156.2		c.218-246T>C		intron	N/A	NP_001293085.1	B7ZAR1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCT5	ENST00000280326.9	TSL:1 MANE Select	c.332-246T>C		intron	N/A	ENSP00000280326.4	P48643-1
	CCT5	ENST00000964556.1		c.332-246T>C		intron	N/A	ENSP00000634615.1
	CCT5	ENST00000964554.1		c.332-246T>C		intron	N/A	ENSP00000634613.1

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

African (AFR) AF: 0.113 AC: 4711 AN: 41534

American (AMR) AF: 0.381 AC: 5829 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.657 AC: 2276 AN: 3466

East Asian (EAS) AF: 0.0576 AC: 299 AN: 5188

South Asian (SAS) AF: 0.325 AC: 1567 AN: 4820

European-Finnish (FIN) AF: 0.650 AC: 6853 AN: 10536

Middle Eastern (MID) AF: 0.483 AC: 142 AN: 294

European-Non Finnish (NFE) AF: 0.643 AC: 43711 AN: 67986

Other (OTH) AF: 0.456 AC: 965 AN: 2114

Alfa AF: 0.582 Hom.: 79183

Bravo AF: 0.407

Asia WGS AF: 0.201 AC: 702 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.2
DANN	Benign	0.64
PhyloP100		0.071
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3846599; hg19: chr5-10255821;