17-34942585-C-T

Variant names:

• chr17-34942585-C-T
• rs1455070895
• NM_006584.4:c.784G>A

Variant summary

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

The NM_006584.4(CCT6B):​c.784G>A​(p.Ala262Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A262P) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CCT6B NM_006584.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.63

Genes affected

CCT6B (HGNC:1621): (chaperonin containing TCP1 subunit 6B) This gene encodes 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. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2015]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCT6B	NM_006584.4	c.784G>A	p.Ala262Thr	missense_variant	Exon 7 of 14	ENST00000314144.10	NP_006575.2
CCT6B	NM_001193529.3	c.673G>A	p.Ala225Thr	missense_variant	Exon 6 of 13		NP_001180458.1
CCT6B	NM_001193530.2	c.649G>A	p.Ala217Thr	missense_variant	Exon 6 of 13		NP_001180459.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCT6B	ENST00000314144.10	c.784G>A	p.Ala262Thr	missense_variant	Exon 7 of 14	1	NM_006584.4	ENSP00000327191.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.060
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.37	.;T;.;D
Eigen	Pathogenic	0.70
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.90	D;D;D;D
M_CAP	Benign	0.058	D
MetaRNN	Uncertain	0.74	D;D;D;D
MetaSVM	Uncertain	0.57	D
MutationAssessor	Pathogenic	3.7	.;H;.;.
PrimateAI	Uncertain	0.54	T
PROVEAN	Uncertain	-3.1	D;D;D;.
REVEL	Uncertain	0.56
Sift	Uncertain	0.0020	D;D;D;.
Sift4G	Uncertain	0.029	D;D;D;D
Polyphen		0.98	.;D;.;.
Vest4		0.47
MutPred		0.50		.;Gain of methylation at K261 (P = 0.1038);.;.;
MVP		0.90
MPC		0.092
ClinPred		0.99	D
GERP RS		4.1
Varity_R		0.87
gMVP		0.52

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: rs1455070895; hg19: chr17-33269604;