Variant 17-34942492-T-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.877A>T(p.Asn293Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000126 in 1,587,116 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

CCT6B
NM_006584.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.43

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:

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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, 0.927

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCT6B	NM_006584.4 linkuse as main transcript	c.877A>T	p.Asn293Tyr	missense_variant	7/14	ENST00000314144.10	NP_006575.2	Q92526-1
CCT6B	NM_001193529.3 linkuse as main transcript	c.766A>T	p.Asn256Tyr	missense_variant	6/13		NP_001180458.1	Q92526-3
CCT6B	NM_001193530.2 linkuse as main transcript	c.742A>T	p.Asn248Tyr	missense_variant	6/13		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.877A>T	p.Asn293Tyr	missense_variant	7/14	1	NM_006584.4	ENSP00000327191.5	Q92526-1
CCT6B	ENST00000421975.7 linkuse as main transcript	c.766A>T	p.Asn256Tyr	missense_variant	6/13	1		ENSP00000398044.3	Q92526-3
CCT6B	ENST00000436961.7 linkuse as main transcript	c.742A>T	p.Asn248Tyr	missense_variant	6/13	2		ENSP00000400917.3	Q92526-2
CCT6B	ENST00000577307.1 linkuse as main transcript	n.2233A>T		non_coding_transcript_exon_variant	2/8	5

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

6.97e-7

AC:

AN:

1434894

Hom.:

Cov.:

AF XY:

0.00000140

AC XY:

AN XY:

713776

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000257

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152222

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74376

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

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

Sep 08, 2024

The c.877A>T (p.N293Y) alteration is located in exon 7 (coding exon 7) of the CCT6B gene. This alteration results from a A to T substitution at nucleotide position 877, causing the asparagine (N) at amino acid position 293 to be replaced by a tyrosine (Y). 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

Pathogenic

0.94

BayesDel_addAF

Pathogenic

0.28

BayesDel_noAF

Pathogenic

0.16

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.65

.;D;.

Eigen

Uncertain

0.58

Eigen_PC

Uncertain

0.43

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Pathogenic

0.98

D;D;D

M_CAP

Uncertain

0.16

MetaRNN

Pathogenic

0.93

D;D;D

MetaSVM

Uncertain

0.44

MutationAssessor

Pathogenic

3.9

.;H;.

PrimateAI

Uncertain

0.69

PROVEAN

Pathogenic

-7.7

D;D;D

REVEL

Pathogenic

0.75

Sift

Pathogenic

0.0

D;D;D

Sift4G

Uncertain

0.032

D;D;D

Polyphen

1.0

.;D;.

Vest4

0.92

MutPred

0.73

.;Loss of catalytic residue at N293 (P = 0.0609);.;

MVP

0.71

MPC

0.41

ClinPred

1.0

GERP RS

3.7

Varity_R

0.96

gMVP

0.87

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over