rs113262482

Positions:

• chr5-10262495-G-A
• chr5-10262495-G-C
• chr5-10262495-G-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BS1 BS2

The NM_012073.5(CCT5):​c.1194G>A​(p.Ala398Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00148 in 1,614,090 control chromosomes in the GnomAD database, including 24 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0073 (15 hom., cov: 33)
  • Exomes 𝑓: 0.00087 (9 hom.)
• Consequence: CCT5 NM_012073.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -2.51

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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BP6: Variant 5-10262495-G-A is Benign according to our data. Variant chr5-10262495-G-A is described in ClinVar as [Benign]. Clinvar id is 465404.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-10262495-G-A is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=-2.51 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00727 (1107/152284) while in subpopulation AFR AF= 0.0244 (1014/41554). AF 95% confidence interval is 0.0232. There are 15 homozygotes in gnomad4. There are 522 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 15 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCT5	NM_012073.5	c.1194G>A	p.Ala398Ala	synonymous_variant	9/11	ENST00000280326.9	NP_036205.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCT5	ENST00000280326.9	c.1194G>A	p.Ala398Ala	synonymous_variant	9/11	1	NM_012073.5	ENSP00000280326.4

Frequencies

GnomAD3 genomes AF: 0.00725 AC: 1103 AN: 152166 Hom.: 15 Cov.: 33

Gnomad AFR AF: 0.0244

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.00294

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000382

Gnomad OTH AF: 0.00669

GnomAD3 exomes AF: 0.00200 AC: 504 AN: 251468 Hom.: 5 AF XY: 0.00138 AC XY: 187 AN XY: 135914

Gnomad AFR exome AF: 0.0234

Gnomad AMR exome AF: 0.00202

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000413

Gnomad OTH exome AF: 0.00114

GnomAD4 exome AF: 0.000875 AC: 1279 AN: 1461806 Hom.: 9 Cov.: 31 AF XY: 0.000776 AC XY: 564 AN XY: 727216

Gnomad4 AFR exome AF: 0.0249

Gnomad4 AMR exome AF: 0.00212

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.0000464

Gnomad4 FIN exome AF: 0.0000187

Gnomad4 NFE exome AF: 0.000180

Gnomad4 OTH exome AF: 0.00217

GnomAD4 genome AF: 0.00727 AC: 1107 AN: 152284 Hom.: 15 Cov.: 33 AF XY: 0.00701 AC XY: 522 AN XY: 74452

Gnomad4 AFR AF: 0.0244

Gnomad4 AMR AF: 0.00294

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.0000942

Gnomad4 NFE AF: 0.000382

Gnomad4 OTH AF: 0.00709

Alfa AF: 0.00113 Hom.: 3

Bravo AF: 0.00768

Asia WGS AF: 0.00173 AC: 6 AN: 3478

EpiCase AF: 0.000218

EpiControl AF: 0.000533

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -

Hereditary sensory and autonomic neuropathy with spastic paraplegia Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Apr 27, 2017	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 18, 2023	- -

not provided Benign:1

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	-0.45
CADD	Benign	5.5
DANN	Benign	0.68

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: rs113262482; hg19: chr5-10262607;