rs2236639

Positions:

• chr22-16591593-A-G
• chr22-16591593-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014406.5(CCT8L2):​c.958T>C​(p.Trp320Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.912 in 1,614,040 control chromosomes in the GnomAD database, including 674,213 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.91 (63659 hom., cov: 32)
  • Exomes 𝑓: 0.91 (610554 hom.)
• Consequence: CCT8L2 NM_014406.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.804

Genes affected

CCT8L2 (HGNC:15553): (chaperonin containing TCP1 subunit 8 like 2) Predicted to enable unfolded protein binding activity. Predicted to be involved in protein folding. Predicted to be part of chaperonin-containing T-complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.19656E-6).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.94 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCT8L2	NM_014406.5	c.958T>C	p.Trp320Arg	missense_variant	1/1	ENST00000359963.4	NP_055221.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCT8L2	ENST00000359963.4	c.958T>C	p.Trp320Arg	missense_variant	1/1		NM_014406.5	ENSP00000353048	P1

Frequencies

GnomAD3 genomes AF: 0.913 AC: 138824 AN: 152098 Hom.: 63611 Cov.: 32

Gnomad AFR AF: 0.948

Gnomad AMI AF: 0.948

Gnomad AMR AF: 0.861

Gnomad ASJ AF: 0.959

Gnomad EAS AF: 0.658

Gnomad SAS AF: 0.901

Gnomad FIN AF: 0.865

Gnomad MID AF: 0.965

Gnomad NFE AF: 0.927

Gnomad OTH AF: 0.913

GnomAD3 exomes AF: 0.883 AC: 221958 AN: 251478 Hom.: 98884 AF XY: 0.888 AC XY: 120730 AN XY: 135912

Gnomad AFR exome AF: 0.947

Gnomad AMR exome AF: 0.783

Gnomad ASJ exome AF: 0.954

Gnomad EAS exome AF: 0.652

Gnomad SAS exome AF: 0.913

Gnomad FIN exome AF: 0.869

Gnomad NFE exome AF: 0.928

Gnomad OTH exome AF: 0.908

GnomAD4 exome AF: 0.912 AC: 1333705 AN: 1461824 Hom.: 610554 Cov.: 69 AF XY: 0.913 AC XY: 663966 AN XY: 727210

Gnomad4 AFR exome AF: 0.948

Gnomad4 AMR exome AF: 0.792

Gnomad4 ASJ exome AF: 0.953

Gnomad4 EAS exome AF: 0.633

Gnomad4 SAS exome AF: 0.909

Gnomad4 FIN exome AF: 0.876

Gnomad4 NFE exome AF: 0.927

Gnomad4 OTH exome AF: 0.915

GnomAD4 genome AF: 0.913 AC: 138927 AN: 152216 Hom.: 63659 Cov.: 32 AF XY: 0.906 AC XY: 67444 AN XY: 74420

Gnomad4 AFR AF: 0.948

Gnomad4 AMR AF: 0.860

Gnomad4 ASJ AF: 0.959

Gnomad4 EAS AF: 0.658

Gnomad4 SAS AF: 0.902

Gnomad4 FIN AF: 0.865

Gnomad4 NFE AF: 0.927

Gnomad4 OTH AF: 0.913

Alfa AF: 0.928 Hom.: 44438

Bravo AF: 0.910

ESP6500AA AF: 0.942 AC: 4151

ESP6500EA AF: 0.932 AC: 8014

ExAC AF: 0.891 AC: 108237

EpiCase AF: 0.933

EpiControl AF: 0.933

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	-0.69	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	6.3
DANN	Benign	0.33
DEOGEN2	Benign	0.10	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.00024	N
LIST_S2	Benign	0.076	T
MetaRNN	Benign	0.0000012	T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	P
PrimateAI	Benign	0.36	T
PROVEAN	Benign	5.5	N
REVEL	Benign	0.12
Sift	Benign	0.60	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.017
MutPred		0.57		Gain of phosphorylation at S319 (P = 0.1023);
MPC		0.27
ClinPred		0.0023	T
GERP RS		0.71
Varity_R		0.065
gMVP		0.30

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: rs2236639; hg19: chr22-17072483; COSMIC: COSV63461921; COSMIC: COSV63461921;