chr17-34932381-G-A

Variant names:

• chr17-34932381-G-A
• NM_006584.4:c.1333C>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_006584.4(CCT6B):​c.1333C>T​(p.Leu445Phe) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CCT6B NM_006584.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.33

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

Our verdict: Uncertain_significance. The variant received 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.1333C>T	p.Leu445Phe	missense_variant	Exon 11 of 14	ENST00000314144.10	NP_006575.2
CCT6B	NM_001193529.3	c.1222C>T	p.Leu408Phe	missense_variant	Exon 10 of 13		NP_001180458.1
CCT6B	NM_001193530.2	c.1198C>T	p.Leu400Phe	missense_variant	Exon 10 of 13		NP_001180459.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCT6B	ENST00000314144.10	c.1333C>T	p.Leu445Phe	missense_variant	Exon 11 of 14	1	NM_006584.4	ENSP00000327191.5
CCT6B	ENST00000421975.7	c.1222C>T	p.Leu408Phe	missense_variant	Exon 10 of 13	1		ENSP00000398044.3
CCT6B	ENST00000436961.7	c.1198C>T	p.Leu400Phe	missense_variant	Exon 10 of 13	2		ENSP00000400917.3
CCT6B	ENST00000577307.1	n.2975C>T		non_coding_transcript_exon_variant	Exon 5 of 8	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 08, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1333C>T (p.L445F) alteration is located in exon 11 (coding exon 11) of the CCT6B gene. This alteration results from a C to T substitution at nucleotide position 1333, causing the leucine (L) at amino acid position 445 to be replaced by a phenylalanine (F). 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	0.42
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.060
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.62	.;D;.
Eigen	Uncertain	0.62
Eigen_PC	Uncertain	0.54
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.91	D;D;D
M_CAP	Uncertain	0.12	D
MetaRNN	Uncertain	0.55	D;D;D
MetaSVM	Uncertain	0.65	D
MutationAssessor	Pathogenic	3.9	.;H;.
PrimateAI	Uncertain	0.68	T
PROVEAN	Uncertain	-3.5	D;D;D
REVEL	Pathogenic	0.67
Sift	Uncertain	0.0060	D;D;D
Sift4G	Uncertain	0.0020	D;D;D
Polyphen		0.71	.;P;.
Vest4		0.44
MutPred		0.61		.;Loss of MoRF binding (P = 0.1437);.;
MVP		0.84
MPC		0.20
ClinPred		0.99	D
GERP RS		3.7
Varity_R		0.90
gMVP		0.46

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: chr17-33259400;