NM_006584.4:c.1277A>G

Variant names:

• chr17-34932437-T-C
• rs752553591
• NM_006584.4:c.1277A>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_006584.4(CCT6B):​c.1277A>G​(p.Lys426Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CCT6B NM_006584.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.75
• 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.

• PM2: Very rare variant in population databases, with high coverage

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.1277A>G	p.Lys426Arg	missense	Exon 11 of 14	NP_006575.2	Q92526-1
	CCT6B	NM_001193529.3		c.1166A>G	p.Lys389Arg	missense	Exon 10 of 13	NP_001180458.1	Q92526-3
	CCT6B	NM_001193530.2		c.1142A>G	p.Lys381Arg	missense	Exon 10 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.1277A>G	p.Lys426Arg	missense	Exon 11 of 14	ENSP00000327191.5	Q92526-1
	CCT6B	ENST00000421975.7	TSL:1	c.1166A>G	p.Lys389Arg	missense	Exon 10 of 13	ENSP00000398044.3	Q92526-3
	CCT6B	ENST00000436961.7	TSL:2	c.1142A>G	p.Lys381Arg	missense	Exon 10 of 13	ENSP00000400917.3	Q92526-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

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	Benign	0.078
BayesDel_addAF	Uncertain	0.032	T
BayesDel_noAF	Benign	-0.19
CADD	Benign	19
DANN	Benign	0.95
DEOGEN2	Benign	0.19	T
Eigen	Benign	-0.32
Eigen_PC	Benign	-0.33
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.036	D
MetaRNN	Uncertain	0.67	D
MetaSVM	Benign	-0.45	T
MutationAssessor	Benign	1.9	L
PhyloP100		5.7
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-2.1	N
REVEL	Uncertain	0.37
Sift	Benign	0.15	T
Sift4G	Benign	0.17	T
Polyphen		0.0020	B
Vest4		0.57
MutPred		0.61		Gain of methylation at K426 (P = 0.0353)
MVP		0.56
MPC		0.066
ClinPred		0.50	T
GERP RS		3.4
Varity_R		0.30
gMVP		0.58

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

Other links and lift over

dbSNP: rs752553591; hg19: chr17-33259456;