Variant 17-34928112-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

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

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.41

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:

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ACMG classification

Classification made for transcript

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
CCT6B	NM_006584.4 linkuse as main transcript	c.1529T>C	p.Val510Ala	missense_variant	14/14	ENST00000314144.10
CCT6B	NM_001193529.3 linkuse as main transcript	c.1418T>C	p.Val473Ala	missense_variant	13/13
CCT6B	NM_001193530.2 linkuse as main transcript	c.1394T>C	p.Val465Ala	missense_variant	13/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCT6B	ENST00000314144.10 linkuse as main transcript	c.1529T>C	p.Val510Ala	missense_variant	14/14	1	NM_006584.4	P1	Q92526-1
CCT6B	ENST00000421975.7 linkuse as main transcript	c.1418T>C	p.Val473Ala	missense_variant	13/13	1			Q92526-3
CCT6B	ENST00000436961.7 linkuse as main transcript	c.1394T>C	p.Val465Ala	missense_variant	13/13	2			Q92526-2
CCT6B	ENST00000577307.1 linkuse as main transcript	n.3171T>C		non_coding_transcript_exon_variant	8/8	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1458784

Hom.:

Cov.:

AF XY:

0.00000276

AC XY:

AN XY:

725784

show subpopulations

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.:

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

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

BayesDel_noAF

Benign

-0.24

CADD

Benign

DANN

Uncertain

0.98

Eigen

Benign

-0.094

Eigen_PC

Benign

0.020

FATHMM_MKL

Uncertain

0.97

LIST_S2

Benign

0.82

T;T;T

M_CAP

Benign

0.048

MetaRNN

Benign

0.29

T;T;T

MetaSVM

Benign

-0.58

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.67

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

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over