rs2244960

Variant names:

• chr5-10263505-G-A
• rs2244960
• NM_012073.5:c.1498+191G>A

Your query was ambiguous. Multiple possible variants found:

• chr5-10263505-G-A
• chr5-10263505-G-C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_012073.5(CCT5):​c.1498+191G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.738 in 152,212 control chromosomes in the GnomAD database, including 43,709 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.74 (43709 hom., cov: 33)
• Consequence: CCT5 NM_012073.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.20
• Publications: 7 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 5-10263505-G-A is Benign according to our data. Variant chr5-10263505-G-A is described in ClinVar as Benign. ClinVar VariationId is 1257274.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.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCT5	NM_012073.5	MANE Select	c.1498+191G>A		intron	N/A	NP_036205.1
	CCT5	NM_001306153.1		c.1435+191G>A		intron	N/A	NP_001293082.1
	CCT5	NM_001306156.2		c.1384+191G>A		intron	N/A	NP_001293085.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCT5	ENST00000280326.9	TSL:1 MANE Select	c.1498+191G>A		intron	N/A	ENSP00000280326.4
	CCT5	ENST00000503026.5	TSL:2	c.1435+191G>A		intron	N/A	ENSP00000423318.1
	CCT5	ENST00000515676.5	TSL:2	c.1384+191G>A		intron	N/A	ENSP00000427297.1

Frequencies

GnomAD3 genomes AF: 0.739 AC: 112334 AN: 152094 Hom.: 43692 Cov.: 33

Gnomad AFR AF: 0.466

Gnomad AMI AF: 0.837

Gnomad AMR AF: 0.810

Gnomad ASJ AF: 0.877

Gnomad EAS AF: 0.865

Gnomad SAS AF: 0.664

Gnomad FIN AF: 0.859

Gnomad MID AF: 0.804

Gnomad NFE AF: 0.856

Gnomad OTH AF: 0.767

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

GnomAD4 genome AF: 0.738 AC: 112391 AN: 152212 Hom.: 43709 Cov.: 33 AF XY: 0.742 AC XY: 55192 AN XY: 74410

African (AFR) AF: 0.466 AC: 19347 AN: 41498

American (AMR) AF: 0.809 AC: 12368 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.877 AC: 3045 AN: 3472

East Asian (EAS) AF: 0.866 AC: 4479 AN: 5174

South Asian (SAS) AF: 0.664 AC: 3207 AN: 4828

European-Finnish (FIN) AF: 0.859 AC: 9102 AN: 10602

Middle Eastern (MID) AF: 0.813 AC: 239 AN: 294

European-Non Finnish (NFE) AF: 0.856 AC: 58217 AN: 68032

Other (OTH) AF: 0.769 AC: 1625 AN: 2114

Alfa AF: 0.787 Hom.: 7933

Bravo AF: 0.727

Asia WGS AF: 0.773 AC: 2686 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.21
DANN	Benign	0.41
PhyloP100		-1.2
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: rs2244960; hg19: chr5-10263617;