chr5-10250409-C-A

Variant names:

• chr5-10250409-C-A
• rs776873105
• NM_012073.5:c.69C>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_012073.5(CCT5):​c.69C>A​(p.Asp23Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,680 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. D23D) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: CCT5 NM_012073.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.114

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.076557755).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCT5	NM_012073.5	c.69C>A	p.Asp23Glu	missense_variant	Exon 1 of 11	ENST00000280326.9	NP_036205.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCT5	ENST00000280326.9	c.69C>A	p.Asp23Glu	missense_variant	Exon 1 of 11	1	NM_012073.5	ENSP00000280326.4

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461680 Hom.: 0 Cov.: 37 AF XY: 0.00 AC XY: 0 AN XY: 727130

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	17
DANN	Benign	0.88
DEOGEN2	Benign	0.11	T;.;T
Eigen	Benign	-0.82
Eigen_PC	Benign	-0.64
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Uncertain	0.89	D;D;T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.077	T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.53	N;.;.
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-0.070	N;N;.
REVEL	Benign	0.23
Sift	Benign	1.0	T;T;.
Sift4G	Benign	1.0	T;T;T
Polyphen		0.0	B;B;.
Vest4		0.089
MutPred		0.22		Gain of methylation at K20 (P = 0.1009);Gain of methylation at K20 (P = 0.1009);Gain of methylation at K20 (P = 0.1009);
MVP		0.38
MPC		0.30
ClinPred		0.068	T
GERP RS		-1.6
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.7
Varity_R		0.099
gMVP		0.31

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: rs776873105; hg19: chr5-10250521;