5-10250616-C-G

Position:

• chr5-10250616-C-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_012073.5(CCT5):​c.105+171C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.826 in 1,440,134 control chromosomes in the GnomAD database, including 498,495 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.74 (43706 hom., cov: 35)
  • Exomes 𝑓: 0.84 (454789 hom.)
• Consequence: CCT5 NM_012073.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.465

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 5-10250616-C-G is Benign according to our data. Variant chr5-10250616-C-G is described in ClinVar as [Benign]. Clinvar id is 1258319.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/exons	MANE	UniProt
CCT5	NM_012073.5	c.105+171C>G		intron_variant		ENST00000280326.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCT5	ENST00000280326.9	c.105+171C>G		intron_variant		1	NM_012073.5	P1

Frequencies

GnomAD3 genomes AF: 0.739 AC: 112350 AN: 152130 Hom.: 43689 Cov.: 35

Gnomad AFR AF: 0.466

Gnomad AMI AF: 0.838

Gnomad AMR AF: 0.809

Gnomad ASJ AF: 0.880

Gnomad EAS AF: 0.865

Gnomad SAS AF: 0.664

Gnomad FIN AF: 0.859

Gnomad MID AF: 0.807

Gnomad NFE AF: 0.855

Gnomad OTH AF: 0.766

GnomAD4 exome AF: 0.837 AC: 1077853 AN: 1287886 Hom.: 454789 Cov.: 50 AF XY: 0.833 AC XY: 520817 AN XY: 625074

Gnomad4 AFR exome AF: 0.444

Gnomad4 AMR exome AF: 0.799

Gnomad4 ASJ exome AF: 0.877

Gnomad4 EAS exome AF: 0.892

Gnomad4 SAS exome AF: 0.664

Gnomad4 FIN exome AF: 0.864

Gnomad4 NFE exome AF: 0.857

Gnomad4 OTH exome AF: 0.823

GnomAD4 genome AF: 0.738 AC: 112409 AN: 152248 Hom.: 43706 Cov.: 35 AF XY: 0.742 AC XY: 55214 AN XY: 74442

Gnomad4 AFR AF: 0.467

Gnomad4 AMR AF: 0.808

Gnomad4 ASJ AF: 0.880

Gnomad4 EAS AF: 0.866

Gnomad4 SAS AF: 0.664

Gnomad4 FIN AF: 0.859

Gnomad4 NFE AF: 0.855

Gnomad4 OTH AF: 0.767

Alfa AF: 0.784 Hom.: 6022

Bravo AF: 0.727

Asia WGS AF: 0.772 AC: 2683 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
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	-0.83
CADD	Benign	7.6
DANN	Benign	0.57

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: rs2607300; hg19: chr5-10250728;