22-16591611-C-A

Variant names:

• chr22-16591611-C-A
• rs375865296
• NM_014406.5:c.940G>T

Variant summary

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

The NM_014406.5(CCT8L2):​c.940G>T​(p.Val314Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,202 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. V314M) has been classified as Uncertain significance.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
• Consequence: CCT8L2 NM_014406.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.02

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 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
CCT8L2	NM_014406.5	c.940G>T	p.Val314Leu	missense_variant	Exon 1 of 1	ENST00000359963.4	NP_055221.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCT8L2	ENST00000359963.4	c.940G>T	p.Val314Leu	missense_variant	Exon 1 of 1	6	NM_014406.5	ENSP00000353048.3

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152202 Hom.: 0 Cov.: 33

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: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251490 Hom.: 0 AF XY: 0.00000736 AC XY: 1 AN XY: 135918

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 87

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152202 Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1 AN XY: 74358

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.39
BayesDel_addAF	Benign	-0.076	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	17
DANN	Benign	0.97
DEOGEN2	Benign	0.32	T
Eigen	Benign	-0.21
Eigen_PC	Benign	-0.27
FATHMM_MKL	Benign	0.56	D
LIST_S2	Benign	0.56	T
M_CAP	Benign	0.014	T
MetaRNN	Uncertain	0.55	D
MetaSVM	Benign	-0.55	T
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-1.9	N
REVEL	Uncertain	0.40
Sift	Benign	0.34	T
Sift4G	Pathogenic	0.0	D
Polyphen		0.39	B
Vest4		0.52
MutPred		0.63		Loss of catalytic residue at Q316 (P = 0.1218);
MVP		0.62
MPC		0.65
ClinPred		0.58	D
GERP RS		2.0
Varity_R		0.23
gMVP		0.53

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs375865296; hg19: chr22-17072501;