Variant chr17-34939685-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_006584.4(CCT6B):c.997G>A(p.Val333Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000415 in 1,612,902 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/23 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000040 ( 0 hom. )

Consequence

CCT6B
NM_006584.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.90

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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
CCT6B	NM_006584.4 linkuse as main transcript	c.997G>A	p.Val333Met	missense_variant	9/14	ENST00000314144.10
CCT6B	NM_001193529.3 linkuse as main transcript	c.886G>A	p.Val296Met	missense_variant	8/13
CCT6B	NM_001193530.2 linkuse as main transcript	c.862G>A	p.Val288Met	missense_variant	8/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCT6B	ENST00000314144.10 linkuse as main transcript	c.997G>A	p.Val333Met	missense_variant	9/14	1	NM_006584.4	P1	Q92526-1
CCT6B	ENST00000421975.7 linkuse as main transcript	c.886G>A	p.Val296Met	missense_variant	8/13	1			Q92526-3
CCT6B	ENST00000436961.7 linkuse as main transcript	c.862G>A	p.Val288Met	missense_variant	8/13	2			Q92526-2
CCT6B	ENST00000577307.1 linkuse as main transcript	n.2353G>A		non_coding_transcript_exon_variant	4/8	5

Frequencies

GnomAD3 genomes

AF:

0.0000526

AC:

AN:

152176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000770

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000637

AC:

AN:

251198

Hom.:

AF XY:

0.0000442

AC XY:

AN XY:

135770

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000707

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000397

AC:

AN:

1460608

Hom.:

Cov.:

AF XY:

0.0000344

AC XY:

AN XY:

726664

show subpopulations

Gnomad4 AFR exome

AF:

0.000120

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000530

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.0000252

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.0000591

AC:

AN:

152294

Hom.:

Cov.:

AF XY:

0.0000671

AC XY:

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000772

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000277

Hom.:

Bravo

AF:

0.0000491

ExAC

AF:

0.0000988

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

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

Apr 18, 2023

The c.997G>A (p.V333M) alteration is located in exon 9 (coding exon 9) of the CCT6B gene. This alteration results from a G to A substitution at nucleotide position 997, causing the valine (V) at amino acid position 333 to be replaced by a methionine (M). 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

0.16

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.44

CADD

Benign

1.6

DANN

Benign

0.26

Eigen

Benign

-1.1

Eigen_PC

Benign

-0.99

FATHMM_MKL

Benign

0.48

LIST_S2

Benign

0.76

T;T;T

M_CAP

Benign

0.029

MetaRNN

Benign

0.041

T;T;T

MetaSVM

Benign

-0.92

MutationTaster

Benign

0.99

N;N;N

PrimateAI

Benign

0.38

PROVEAN

Benign

1.1

N;N;N

REVEL

Benign

0.17

Sift

Benign

0.67

T;T;T

Sift4G

Benign

0.55

T;T;T

Polyphen

0.054

.;B;.

Vest4

0.23

MutPred

0.65

.;Loss of catalytic residue at V333 (P = 0.1651);.;

MVP

0.19

MPC

0.093

ClinPred

0.036

GERP RS

-2.1

Varity_R

0.072

gMVP

0.44

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.21

Details are displayed if max score is > 0.2

DS_AL_spliceai

0.21

Position offset: 28

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