chr17-34942585-C-G

Variant names:

• chr17-34942585-C-G
• rs1455070895
• NM_006584.4:c.784G>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PP3_Moderate

The NM_006584.4(CCT6B):​c.784G>C​(p.Ala262Pro) variant causes a missense change. The variant allele was found at a frequency of 0.0000155 in 1,608,164 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 0.000046 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000012 (0 hom.)
• Consequence: CCT6B NM_006584.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.63
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.852

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006584.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCT6B	NM_006584.4	MANE Select	c.784G>C	p.Ala262Pro	missense	Exon 7 of 14	NP_006575.2	Q92526-1
	CCT6B	NM_001193529.3		c.673G>C	p.Ala225Pro	missense	Exon 6 of 13	NP_001180458.1	Q92526-3
	CCT6B	NM_001193530.2		c.649G>C	p.Ala217Pro	missense	Exon 6 of 13	NP_001180459.1	Q92526-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCT6B	ENST00000314144.10	TSL:1 MANE Select	c.784G>C	p.Ala262Pro	missense	Exon 7 of 14	ENSP00000327191.5	Q92526-1
	CCT6B	ENST00000421975.7	TSL:1	c.673G>C	p.Ala225Pro	missense	Exon 6 of 13	ENSP00000398044.3	Q92526-3
	CCT6B	ENST00000436961.7	TSL:2	c.649G>C	p.Ala217Pro	missense	Exon 6 of 13	ENSP00000400917.3	Q92526-2

Frequencies

GnomAD3 genomes AF: 0.0000460 AC: 7 AN: 152110 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000327

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: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000404 AC: 1 AN: 247508 AF XY: 0.00

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000165

GnomAD4 exome AF: 0.0000124 AC: 18 AN: 1456054 Hom.: 0 Cov.: 28 AF XY: 0.00000690 AC XY: 5 AN XY: 724514

African (AFR) AF: 0.00 AC: 0 AN: 33144

American (AMR) AF: 0.0000229 AC: 1 AN: 43712

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26080

East Asian (EAS) AF: 0.00 AC: 0 AN: 39540

South Asian (SAS) AF: 0.00 AC: 0 AN: 85210

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53298

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5662

European-Non Finnish (NFE) AF: 0.0000135 AC: 15 AN: 1109266

Other (OTH) AF: 0.0000333 AC: 2 AN: 60142

GnomAD4 genome AF: 0.0000460 AC: 7 AN: 152110 Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3 AN XY: 74302

African (AFR) AF: 0.00 AC: 0 AN: 41418

American (AMR) AF: 0.000327 AC: 5 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5198

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10596

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68016

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.0000282 Hom.: 0

Bravo AF: 0.0000831

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.95
BayesDel_addAF	Pathogenic	0.25	D
BayesDel_noAF	Uncertain	0.12
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.62	D
Eigen	Uncertain	0.47
Eigen_PC	Uncertain	0.43
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.080	D
MetaRNN	Pathogenic	0.85	D
MetaSVM	Uncertain	0.50	D
MutationAssessor	Pathogenic	3.7	H
PhyloP100		5.6
PrimateAI	Uncertain	0.59	T
PROVEAN	Uncertain	-4.3	D
REVEL	Pathogenic	0.69
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0080	D
Polyphen		0.57	P
Vest4		0.69
MutPred		0.68		Gain of loop (P = 0.0121)
MVP		0.89
MPC		0.13
ClinPred		0.99	D
GERP RS		4.1
Varity_R		0.98
gMVP		0.86
Mutation Taster		=20/80	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1455070895; hg19: chr17-33269604;