rs2244964

Variant names:

• chr5-10263613-G-A
• rs2244964
• NM_012073.5:c.1498+299G>A

Your query was ambiguous. Multiple possible variants found:

• chr5-10263613-G-A
• chr5-10263613-G-C
• chr5-10263613-G-T

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.1498+299G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.737 in 152,170 control chromosomes in the GnomAD database, including 43,623 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.74 (43623 hom., cov: 33)
• Consequence: CCT5 NM_012073.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.50
• Publications: 16 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=-0.91).
• BP6: Variant 5-10263613-G-A is Benign according to our data. Variant chr5-10263613-G-A is described in ClinVar as Benign. ClinVar VariationId is 1236765.Status of the report is criteria_provided_single_submitter, 1 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	c.1498+299G>A		intron_variant	Intron 10 of 10	ENST00000280326.9	NP_036205.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCT5	ENST00000280326.9	c.1498+299G>A		intron_variant	Intron 10 of 10	1	NM_012073.5	ENSP00000280326.4

Frequencies

GnomAD3 genomes AF: 0.738 AC: 112161 AN: 152052 Hom.: 43606 Cov.: 33

Gnomad AFR AF: 0.463

Gnomad AMI AF: 0.838

Gnomad AMR AF: 0.809

Gnomad ASJ AF: 0.877

Gnomad EAS AF: 0.866

Gnomad SAS AF: 0.663

Gnomad FIN AF: 0.859

Gnomad MID AF: 0.809

Gnomad NFE AF: 0.856

Gnomad OTH AF: 0.766

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

GnomAD4 genome AF: 0.737 AC: 112218 AN: 152170 Hom.: 43623 Cov.: 33 AF XY: 0.741 AC XY: 55101 AN XY: 74384

African (AFR) AF: 0.463 AC: 19183 AN: 41456

American (AMR) AF: 0.809 AC: 12368 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.877 AC: 3043 AN: 3470

East Asian (EAS) AF: 0.866 AC: 4491 AN: 5186

South Asian (SAS) AF: 0.663 AC: 3202 AN: 4826

European-Finnish (FIN) AF: 0.859 AC: 9095 AN: 10590

Middle Eastern (MID) AF: 0.818 AC: 239 AN: 292

European-Non Finnish (NFE) AF: 0.856 AC: 58212 AN: 68032

Other (OTH) AF: 0.768 AC: 1621 AN: 2112

Alfa AF: 0.810 Hom.: 24341

Bravo AF: 0.726

Asia WGS AF: 0.773 AC: 2686 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 18, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.062
DANN	Benign	0.34
PhyloP100		-3.5
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: rs2244964; hg19: chr5-10263725;