17-34929013-T-G

Variant names:

• chr17-34929013-T-G
• rs764176435
• NM_006584.4:c.1472A>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006584.4(CCT6B):​c.1472A>C​(p.Asp491Ala) variant causes a missense change. The variant allele was found at a frequency of 0.0000305 in 1,609,042 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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. D491G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000032 (0 hom.)
• Consequence: CCT6B NM_006584.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.74
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24500227).

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.1472A>C	p.Asp491Ala	missense	Exon 13 of 14	NP_006575.2	Q92526-1
	CCT6B	NM_001193529.3		c.1361A>C	p.Asp454Ala	missense	Exon 12 of 13	NP_001180458.1	Q92526-3
	CCT6B	NM_001193530.2		c.1337A>C	p.Asp446Ala	missense	Exon 12 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.1472A>C	p.Asp491Ala	missense	Exon 13 of 14	ENSP00000327191.5	Q92526-1
	CCT6B	ENST00000421975.7	TSL:1	c.1361A>C	p.Asp454Ala	missense	Exon 12 of 13	ENSP00000398044.3	Q92526-3
	CCT6B	ENST00000436961.7	TSL:2	c.1337A>C	p.Asp446Ala	missense	Exon 12 of 13	ENSP00000400917.3	Q92526-2

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152228 Hom.: 0 Cov.: 32

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: 0.0000294

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000323 AC: 47 AN: 1456814 Hom.: 0 Cov.: 27 AF XY: 0.0000276 AC XY: 20 AN XY: 724806

African (AFR) AF: 0.00 AC: 0 AN: 33394

American (AMR) AF: 0.00 AC: 0 AN: 44676

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 39570

South Asian (SAS) AF: 0.00 AC: 0 AN: 85508

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53276

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5748

European-Non Finnish (NFE) AF: 0.0000415 AC: 46 AN: 1108366

Other (OTH) AF: 0.0000166 AC: 1 AN: 60196

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152228 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74380

African (AFR) AF: 0.00 AC: 0 AN: 41458

American (AMR) AF: 0.00 AC: 0 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5204

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

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

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68034

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000658 Hom.: 0

Bravo AF: 0.0000189

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
BayesDel_addAF	Benign	-0.00011	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	21
DANN	Benign	0.88
DEOGEN2	Benign	0.12	T
Eigen	Benign	-0.10
Eigen_PC	Benign	0.090
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.66	T
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-0.67	T
MutationAssessor	Benign	1.5	L
PhyloP100		4.7
PrimateAI	Benign	0.39	T
PROVEAN	Uncertain	-2.6	D
REVEL	Benign	0.24
Sift	Benign	0.76	T
Sift4G	Benign	0.74	T
Polyphen		0.0	B
Vest4		0.34
MVP		0.71
MPC		0.095
ClinPred		0.88	D
GERP RS		4.9
Varity_R		0.38
gMVP		0.27
Mutation Taster		=62/38	polymorphism

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: rs764176435; hg19: chr17-33256032;