22-16591729-G-A

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_014406.5(CCT8L2):c.822C>T(p.Ser274=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00217 in 1,614,154 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0018 (1 hom., cov: 33)
  • Exomes 𝑓: 0.0022 (8 hom.)
• Consequence: CCT8L2 NM_014406.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.18

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 -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 22-16591729-G-A is Benign according to our data. Variant chr22-16591729-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2652839.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.18 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCT8L2	NM_014406.5	c.822C>T	p.Ser274=	synonymous_variant	1/1	ENST00000359963.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCT8L2	ENST00000359963.4	c.822C>T	p.Ser274=	synonymous_variant	1/1		NM_014406.5	P1

Frequencies

GnomAD3 genomes AF: 0.00177 AC: 269 AN: 152144 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.000773

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000524

Gnomad ASJ AF: 0.0133

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00262

Gnomad OTH AF: 0.00143

GnomAD3 exomes AF: 0.00193 AC: 485 AN: 251482 Hom.: 1 AF XY: 0.00183 AC XY: 249 AN XY: 135918

Gnomad AFR exome AF: 0.000677

Gnomad AMR exome AF: 0.000434

Gnomad ASJ exome AF: 0.0110

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.000277

Gnomad NFE exome AF: 0.00288

Gnomad OTH exome AF: 0.00212

GnomAD4 exome AF: 0.00221 AC: 3232 AN: 1461892 Hom.: 8 Cov.: 87 AF XY: 0.00210 AC XY: 1528 AN XY: 727248

Gnomad4 AFR exome AF: 0.000926

Gnomad4 AMR exome AF: 0.000492

Gnomad4 ASJ exome AF: 0.0114

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000104

Gnomad4 FIN exome AF: 0.000337

Gnomad4 NFE exome AF: 0.00242

Gnomad4 OTH exome AF: 0.00268

GnomAD4 genome AF: 0.00177 AC: 269 AN: 152262 Hom.: 1 Cov.: 33 AF XY: 0.00146 AC XY: 109 AN XY: 74442

Gnomad4 AFR AF: 0.000770

Gnomad4 AMR AF: 0.000523

Gnomad4 ASJ AF: 0.0133

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.0000942

Gnomad4 NFE AF: 0.00262

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.00315 Hom.: 0

Bravo AF: 0.00178

EpiCase AF: 0.00224

EpiControl AF: 0.00172

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Nov 01, 2022

CCT8L2: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.39
Dann	Benign	0.72

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: rs145079801; hg19: chr22-17072619;