Variant 17-34954439-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_006584.4(CCT6B):c.497A>T(p.Asp166Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000561 in 1,605,388 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000028 ( 0 hom. )

Consequence

CCT6B
NM_006584.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.68

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 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.81

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
CCT6B	NM_006584.4 linkuse as main transcript	c.497A>T	p.Asp166Val	missense_variant	4/14	ENST00000314144.10
CCT6B	NM_001193529.3 linkuse as main transcript	c.497A>T	p.Asp166Val	missense_variant	4/13
CCT6B	NM_001193530.2 linkuse as main transcript	c.362A>T	p.Asp121Val	missense_variant	3/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCT6B	ENST00000314144.10 linkuse as main transcript	c.497A>T	p.Asp166Val	missense_variant	4/14	1	NM_006584.4	P1	Q92526-1
CCT6B	ENST00000421975.7 linkuse as main transcript	c.497A>T	p.Asp166Val	missense_variant	4/13	1			Q92526-3
CCT6B	ENST00000436961.7 linkuse as main transcript	c.362A>T	p.Asp121Val	missense_variant	3/13	2			Q92526-2
CCT6B	ENST00000585073.1 linkuse as main transcript	c.71A>T	p.Asp24Val	missense_variant	2/5	3

Frequencies

GnomAD3 genomes

AF:

0.0000328

AC:

AN:

152238

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000413

AC:

AN:

241968

Hom.:

AF XY:

0.00000763

AC XY:

AN XY:

131076

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000315

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

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:

0.00000275

AC:

AN:

1453150

Hom.:

Cov.:

AF XY:

0.00000415

AC XY:

AN XY:

722702

show subpopulations

Gnomad4 AFR exome

AF:

0.0000305

Gnomad4 AMR exome

AF:

0.0000234

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:

0.00

Gnomad4 OTH exome

AF:

0.0000333

GnomAD4 genome

AF:

0.0000328

AC:

AN:

152238

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74368

show subpopulations

Gnomad4 AFR

AF:

0.0000482

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000227

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Uncertain

0.14

BayesDel_noAF

Uncertain

0.060

CADD

Benign

DANN

Uncertain

0.98

Eigen

Uncertain

0.32

Eigen_PC

Uncertain

0.28

FATHMM_MKL

Uncertain

0.95

LIST_S2

Pathogenic

0.98

D;D;D;D

M_CAP

Uncertain

0.25

MetaRNN

Pathogenic

0.81

D;D;D;D

MetaSVM

Uncertain

0.29

MutationAssessor

Pathogenic

3.4

M;M;.;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Benign

0.38

PROVEAN

Pathogenic

-7.6

D;D;D;.

REVEL

Pathogenic

0.67

Sift

Uncertain

0.013

D;D;D;.

Sift4G

Uncertain

0.019

D;D;D;D

Polyphen

0.35

.;B;.;.

Vest4

0.72

MutPred

0.60

Loss of helix (P = 0.0104);Loss of helix (P = 0.0104);.;.;

MVP

0.67

MPC

0.26

ClinPred

0.99

GERP RS

4.1

Varity_R

0.89

gMVP

0.78

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

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over