17-34942847-A-G

Position:

• chr17-34942847-A-G

Variant summary

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

The NM_006584.4(CCT6B):​c.674T>C​(p.Val225Ala) 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.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CCT6B NM_006584.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.88

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.674T>C	p.Val225Ala	missense_variant	6/14	ENST00000314144.10	NP_006575.2
CCT6B	NM_001193530.2	c.539T>C	p.Val180Ala	missense_variant	5/13		NP_001180459.1
CCT6B	NM_001193529.3	c.615-204T>C		intron_variant			NP_001180458.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCT6B	ENST00000314144.10	c.674T>C	p.Val225Ala	missense_variant	6/14	1	NM_006584.4	ENSP00000327191.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

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

Dec 06, 2024

The c.674T>C (p.V225A) alteration is located in exon 6 (coding exon 6) of the CCT6B gene. This alteration results from a T to C substitution at nucleotide position 674, causing the valine (V) at amino acid position 225 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	Benign	0.20
BayesDel_addAF	Uncertain	0.033	T
BayesDel_noAF	Benign	-0.19
CADD	Benign	22
DANN	Benign	0.96
DEOGEN2	Benign	0.19	T;.;D
Eigen	Benign	-0.30
Eigen_PC	Benign	-0.25
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.97	D;D;D
M_CAP	Benign	0.028	D
MetaRNN	Uncertain	0.66	D;D;D
MetaSVM	Benign	-0.66	T
MutationAssessor	Pathogenic	3.0	M;.;.
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-2.0	N;N;.
REVEL	Uncertain	0.32
Sift	Benign	0.12	T;T;.
Sift4G	Benign	0.080	T;T;T
Polyphen		0.013	B;.;.
Vest4		0.62
MutPred		0.73		Gain of loop (P = 0.0312);.;.;
MVP		0.55
MPC		0.11
ClinPred		0.91	D
GERP RS		3.1
Varity_R		0.27
gMVP		0.75

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-33269866;