22-16591593-A-G

Variant names:

• chr22-16591593-A-G
• rs2236639
• NM_014406.5:c.958T>C

Variant summary

Our verdict is Benign. The variant received -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. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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
• Publications: 21 publications found

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]

ENSG00000290416 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014406.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCT8L2	NM_014406.5	MANE Select	c.958T>C	p.Trp320Arg	missense	Exon 1 of 1	NP_055221.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCT8L2	ENST00000359963.4	TSL:6 MANE Select	c.958T>C	p.Trp320Arg	missense	Exon 1 of 1	ENSP00000353048.3
	ENSG00000290416	ENST00000472972.2	TSL:2	n.287-6899T>C		intron	N/A
	ENSG00000290416	ENST00000725389.1		n.112-6899T>C		intron	N/A

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

GnomAD2 exomes AF: 0.883 AC: 221958 AN: 251478 AF XY: 0.888

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 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

African (AFR) AF: 0.948 AC: 31739 AN: 33478

American (AMR) AF: 0.792 AC: 35439 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.953 AC: 24901 AN: 26136

East Asian (EAS) AF: 0.633 AC: 25111 AN: 39698

South Asian (SAS) AF: 0.909 AC: 78372 AN: 86252

European-Finnish (FIN) AF: 0.876 AC: 46812 AN: 53420

Middle Eastern (MID) AF: 0.950 AC: 5478 AN: 5768

European-Non Finnish (NFE) AF: 0.927 AC: 1030581 AN: 1111954

Other (OTH) AF: 0.915 AC: 55272 AN: 60396

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

African (AFR) AF: 0.948 AC: 39399 AN: 41568

American (AMR) AF: 0.860 AC: 13142 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.959 AC: 3330 AN: 3472

East Asian (EAS) AF: 0.658 AC: 3392 AN: 5156

South Asian (SAS) AF: 0.902 AC: 4356 AN: 4830

European-Finnish (FIN) AF: 0.865 AC: 9168 AN: 10596

Middle Eastern (MID) AF: 0.959 AC: 282 AN: 294

European-Non Finnish (NFE) AF: 0.927 AC: 63063 AN: 67996

Other (OTH) AF: 0.913 AC: 1930 AN: 2114

Alfa AF: 0.930 Hom.: 53637

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 v4.9

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
PhyloP100		0.80
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
Mutation Taster		=100/0	polymorphism (auto)

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