Variant 17-34931051-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_006584.4(CCT6B):c.1348G>T(p.Val450Phe) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.0000128 in 1,249,462 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000013 ( 0 hom. )

Consequence

CCT6B
NM_006584.4 missense, splice_region

Scores

Splicing: ADA: 0.9999

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.04

Variant links:

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 links:

CCT6B (HGNC:):

CCT6B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.876

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCT6B	NM_006584.4 linkuse as main transcript	c.1348G>T	p.Val450Phe	missense_variant, splice_region_variant	12/14	ENST00000314144.10	NP_006575.2	Q92526-1
CCT6B	NM_001193529.3 linkuse as main transcript	c.1237G>T	p.Val413Phe	missense_variant, splice_region_variant	11/13		NP_001180458.1	Q92526-3
CCT6B	NM_001193530.2 linkuse as main transcript	c.1213G>T	p.Val405Phe	missense_variant, splice_region_variant	11/13		NP_001180459.1	Q92526-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CCT6B	ENST00000314144.10 linkuse as main transcript	c.1348G>T	p.Val450Phe	missense_variant, splice_region_variant	12/14	1	NM_006584.4	ENSP00000327191.5	Q92526-1
CCT6B	ENST00000421975.7 linkuse as main transcript	c.1237G>T	p.Val413Phe	missense_variant, splice_region_variant	11/13	1		ENSP00000398044.3	Q92526-3
CCT6B	ENST00000436961.7 linkuse as main transcript	c.1213G>T	p.Val405Phe	missense_variant, splice_region_variant	11/13	2		ENSP00000400917.3	Q92526-2
CCT6B	ENST00000577307.1 linkuse as main transcript	n.2990G>T		splice_region_variant, non_coding_transcript_exon_variant	6/8	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000256

AC:

AN:

234702

Hom.:

AF XY:

0.0000235

AC XY:

AN XY:

127900

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000329

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000300

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000128

AC:

AN:

1249462

Hom.:

Cov.:

AF XY:

0.0000112

AC XY:

AN XY:

625736

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000248

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000294

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000315

Gnomad4 OTH exome

AF:

0.0000194

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000412

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 02, 2023

The c.1348G>T (p.V450F) alteration is located in exon 12 (coding exon 12) of the CCT6B gene. This alteration results from a G to T substitution at nucleotide position 1348, causing the valine (V) at amino acid position 450 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

0.47

BayesDel_addAF

Uncertain

0.16

BayesDel_noAF

Pathogenic

0.31

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.43

.;T;.

Eigen

Pathogenic

0.81

Eigen_PC

Pathogenic

0.76

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Pathogenic

0.99

D;D;D

M_CAP

Uncertain

0.23

MetaRNN

Pathogenic

0.88

D;D;D

MetaSVM

Uncertain

0.49

MutationAssessor

Pathogenic

3.1

.;M;.

PrimateAI

Uncertain

0.63

PROVEAN

Uncertain

-3.3

D;D;D

REVEL

Pathogenic

0.85

Sift

Uncertain

0.0010

D;D;D

Sift4G

Uncertain

0.0040

D;D;D

Polyphen

0.97

.;D;.

Vest4

0.85

MutPred

0.68

.;Gain of helix (P = 0.2059);.;

MVP

0.90

MPC

0.46

ClinPred

0.89

GERP RS

4.8

Varity_R

0.96

gMVP

0.83

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

1.0

dbscSNV1_RF

Pathogenic

0.98

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over