dbSNP rs1455070895: CCT6B:p.Ala262Ser (chr17-34942585-C-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

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

The NM_006584.4(CCT6B):c.784G>T(p.Ala262Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000000687 in 1,456,054 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A262P) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

CCT6B
NM_006584.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.63

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=0.3314321).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCT6B	NM_006584.4 link	c.784G>T	p.Ala262Ser	missense_variant	Exon 7 of 14	ENST00000314144.10	NP_006575.2	Q92526-1
CCT6B	NM_001193529.3 link	c.673G>T	p.Ala225Ser	missense_variant	Exon 6 of 13		NP_001180458.1	Q92526-3
CCT6B	NM_001193530.2 link	c.649G>T	p.Ala217Ser	missense_variant	Exon 6 of 13		NP_001180459.1	Q92526-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCT6B	ENST00000314144.10 link	c.784G>T	p.Ala262Ser	missense_variant	Exon 7 of 14	1	NM_006584.4	ENSP00000327191.5		Q92526-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000404

AC:

AN:

247508

Hom.:

AF XY:

0.00

AC XY:

AN XY:

133902

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000465

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.87e-7

AC:

AN:

1456054

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

724514

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:

0.0000188

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Uncertain

0.041

BayesDel_noAF

Benign

-0.18

CADD

Benign

DANN

Benign

0.91

DEOGEN2

Benign

0.14

.;T;.;T

Eigen

Benign

-0.11

Eigen_PC

Benign

0.021

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.95

D;D;D;D

M_CAP

Benign

0.039

MetaRNN

Benign

0.33

T;T;T;T

MetaSVM

Benign

-0.65

MutationAssessor

Benign

1.6

.;L;.;.

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-1.8

N;N;N;.

REVEL

Uncertain

0.41

Sift

Benign

0.70

T;T;T;.

Sift4G

Benign

0.78

T;T;T;T

Polyphen

0.15

.;B;.;.

Vest4

0.60

MutPred

0.51

.;Gain of phosphorylation at A262 (P = 0.0186);.;.;

MVP

0.74

MPC

0.077

ClinPred

0.31

GERP RS

4.1

Varity_R

0.41

gMVP

0.48

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