17-34928112-A-G

Position:

• chr17-34928112-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_006584.4(CCT6B):​c.1529T>C​(p.Val510Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,458,784 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: CCT6B NM_006584.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.41

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.29324412).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCT6B	NM_006584.4	c.1529T>C	p.Val510Ala	missense_variant	14/14	ENST00000314144.10	NP_006575.2
CCT6B	NM_001193529.3	c.1418T>C	p.Val473Ala	missense_variant	13/13		NP_001180458.1
CCT6B	NM_001193530.2	c.1394T>C	p.Val465Ala	missense_variant	13/13		NP_001180459.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCT6B	ENST00000314144.10	c.1529T>C	p.Val510Ala	missense_variant	14/14	1	NM_006584.4	ENSP00000327191.5
CCT6B	ENST00000421975.7	c.1418T>C	p.Val473Ala	missense_variant	13/13	1		ENSP00000398044.3
CCT6B	ENST00000436961.7	c.1394T>C	p.Val465Ala	missense_variant	13/13	2		ENSP00000400917.3
CCT6B	ENST00000577307.1	n.3171T>C		non_coding_transcript_exon_variant	8/8	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1458784 Hom.: 0 Cov.: 28 AF XY: 0.00000276 AC XY: 2 AN XY: 725784

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.: 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

Oct 12, 2022

The c.1529T>C (p.V510A) alteration is located in exon 14 (coding exon 14) of the CCT6B gene. This alteration results from a T to C substitution at nucleotide position 1529, causing the valine (V) at amino acid position 510 to be replaced by an alanine (A). 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	Uncertain	0.40
BayesDel_addAF	Benign	-0.0041	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.35	.;T;.
Eigen	Benign	-0.094
Eigen_PC	Benign	0.020
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Benign	0.82	T;T;T
M_CAP	Benign	0.048	D
MetaRNN	Benign	0.29	T;T;T
MetaSVM	Benign	-0.58	T
MutationAssessor	Uncertain	2.6	.;M;.
PrimateAI	Uncertain	0.67	T
PROVEAN	Uncertain	-3.2	D;D;D
REVEL	Uncertain	0.40
Sift	Benign	0.14	T;T;T
Sift4G	Benign	0.30	T;T;T
Polyphen		0.0060	.;B;.
Vest4		0.33
MutPred		0.50		.;Loss of stability (P = 0.0567);.;
MVP		0.46
MPC		0.10
ClinPred		0.91	D
GERP RS		4.0
Varity_R		0.33
gMVP		0.65

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		Details are displayed if max score is > 0.2

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: chr17-33255131;