chr21-29063356-C-G

Variant names:

• chr21-29063356-C-G
• rs372863710
• NM_006585.4:c.937G>C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_006585.4(CCT8):​c.937G>C​(p.Val313Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000117 in 1,457,496 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000012 (0 hom.)
• Consequence: CCT8 NM_006585.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.66

Genes affected

CCT8 (HGNC:1623): (chaperonin containing TCP1 subunit 8) This gene encodes the theta subunit of the CCT chaperonin, which is abundant in the eukaryotic cytosol and may be involved in the transport and assembly of newly synthesized proteins. Alternative splicing results in multiple transcript variants of this gene. A pseudogene related to this gene is located on chromosome 1. [provided by RefSeq, Sep 2013]

ENSG00000286018 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCT8	NM_006585.4	c.937G>C	p.Val313Leu	missense_variant	Exon 8 of 15	ENST00000286788.9	NP_006576.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCT8	ENST00000286788.9	c.937G>C	p.Val313Leu	missense_variant	Exon 8 of 15	1	NM_006585.4	ENSP00000286788.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000161 AC: 4 AN: 248524 Hom.: 0 AF XY: 0.0000149 AC XY: 2 AN XY: 134248

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000164

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000886

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000117 AC: 17 AN: 1457496 Hom.: 0 Cov.: 32 AF XY: 0.00000966 AC XY: 7 AN XY: 724946

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000403

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ExAC AF: 0.0000247 AC: 3

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.34
BayesDel_addAF	Uncertain	0.023	T
BayesDel_noAF	Uncertain	0.060
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.60	.;D;.
Eigen	Uncertain	0.39
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Pathogenic	0.98	D;D;D
M_CAP	Benign	0.035	D
MetaRNN	Uncertain	0.64	D;D;D
MetaSVM	Benign	-0.49	T
MutationAssessor	Benign	1.8	.;L;.
PrimateAI	Uncertain	0.72	T
PROVEAN	Uncertain	-3.0	D;D;.
REVEL	Uncertain	0.55
Sift	Benign	0.51	T;T;.
Sift4G	Benign	0.52	T;T;T
Polyphen		0.049	.;B;.
Vest4		0.64
MutPred		0.69		.;Loss of MoRF binding (P = 0.096);.;
MVP		0.85
MPC		0.53
ClinPred		0.60	D
GERP RS		5.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.78
gMVP		0.74

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

Other links and lift over

dbSNP: rs372863710; hg19: chr21-30435677;