chr17-34942587-T-C

Position:

• chr17-34942587-T-C

Variant summary

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

The NM_006584.4(CCT6B):​c.782A>G​(p.Lys261Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000275 in 1,456,068 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/23 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: CCT6B NM_006584.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.93

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]

CCT6B (HGNC:):

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/exons	MANE	Protein	UniProt
CCT6B	NM_006584.4	c.782A>G	p.Lys261Arg	missense_variant	7/14	ENST00000314144.10	NP_006575.2
CCT6B	NM_001193529.3	c.671A>G	p.Lys224Arg	missense_variant	6/13		NP_001180458.1
CCT6B	NM_001193530.2	c.647A>G	p.Lys216Arg	missense_variant	6/13		NP_001180459.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCT6B	ENST00000314144.10	c.782A>G	p.Lys261Arg	missense_variant	7/14	1	NM_006584.4	ENSP00000327191.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000275 AC: 4 AN: 1456068 Hom.: 0 Cov.: 28 AF XY: 0.00000414 AC XY: 3 AN XY: 724494

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: 0.00000270

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 26, 2024

The c.782A>G (p.K261R) alteration is located in exon 7 (coding exon 7) of the CCT6B gene. This alteration results from a A to G substitution at nucleotide position 782, causing the lysine (K) at amino acid position 261 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.076	.;T;.;T
Eigen	Benign	-0.49
Eigen_PC	Benign	-0.38
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Uncertain	0.87	D;D;D;D
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.13	T;T;T;T
MetaSVM	Benign	-0.78	T
MutationAssessor	Benign	1.4	.;L;.;.
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-0.96	N;N;N;.
REVEL	Benign	0.055
Sift	Benign	0.21	T;T;T;.
Sift4G	Benign	0.27	T;T;T;T
Polyphen		0.015	.;B;.;.
Vest4		0.11
MutPred		0.46		.;Loss of methylation at K261 (P = 0.0253);.;.;
MVP		0.58
MPC		0.074
ClinPred		0.29	T
GERP RS		2.9
Varity_R		0.20
gMVP		0.39

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.27		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.27		Position offset: 5

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-33269606;