Variant 22-16591521-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_014406.5(CCT8L2):c.1030C>A(p.Pro344Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00718 in 1,614,178 control chromosomes in the GnomAD database, including 56 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0061 ( 4 hom., cov: 33)

Exomes 𝑓: 0.0073 ( 52 hom. )

Consequence

CCT8L2
NM_014406.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.710

Variant links:

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]

CCT8L2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.017612249).

BP6

Variant 22-16591521-G-T is Benign according to our data. Variant chr22-16591521-G-T is described in ClinVar as [Benign]. Clinvar id is 782172.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCT8L2	NM_014406.5 linkuse as main transcript	c.1030C>A	p.Pro344Thr	missense_variant	1/1	ENST00000359963.4	NP_055221.1	Q96SF2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCT8L2	ENST00000359963.4 linkuse as main transcript	c.1030C>A	p.Pro344Thr	missense_variant	1/1	6	NM_014406.5	ENSP00000353048.3		Q96SF2

Frequencies

GnomAD3 genomes

AF:

0.00615

AC:

936

AN:

152180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00164

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00622

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.0148

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00863

Gnomad OTH

AF:

0.00573

GnomAD3 exomes

AF:

0.00535

AC:

1346

AN:

251456

Hom.:

AF XY:

0.00538

AC XY:

731

AN XY:

135916

show subpopulations

Gnomad AFR exome

AF:

0.00105

Gnomad AMR exome

AF:

0.00185

Gnomad ASJ exome

AF:

0.00119

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00199

Gnomad FIN exome

AF:

0.0132

Gnomad NFE exome

AF:

0.00765

Gnomad OTH exome

AF:

0.00603

GnomAD4 exome

AF:

0.00729

AC:

10655

AN:

1461880

Hom.:

Cov.:

AF XY:

0.00717

AC XY:

5213

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.000717

Gnomad4 AMR exome

AF:

0.00233

Gnomad4 ASJ exome

AF:

0.00138

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00202

Gnomad4 FIN exome

AF:

0.0132

Gnomad4 NFE exome

AF:

0.00824

Gnomad4 OTH exome

AF:

0.00700

GnomAD4 genome

AF:

0.00614

AC:

935

AN:

152298

Hom.:

Cov.:

AF XY:

0.00630

AC XY:

469

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.00164

Gnomad4 AMR

AF:

0.00621

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00124

Gnomad4 FIN

AF:

0.0148

Gnomad4 NFE

AF:

0.00863

Gnomad4 OTH

AF:

0.00567

Alfa

AF:

0.00697

Hom.:

Bravo

AF:

0.00534

TwinsUK

AF:

0.00755

AC:

ALSPAC

AF:

0.00960

AC:

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00802

AC:

ExAC

AF:

0.00509

AC:

618

EpiCase

AF:

0.00709

EpiControl

AF:

0.00652

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Nov 08, 2017	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.092

Eigen

Benign

-0.54

Eigen_PC

Benign

-0.66

FATHMM_MKL

Benign

0.011

LIST_S2

Benign

0.54

MetaRNN

Benign

0.018

MetaSVM

Benign

-0.73

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-1.1

REVEL

Benign

0.18

Sift

Benign

0.33

Sift4G

Uncertain

0.022

Polyphen

0.45

Vest4

0.24

MVP

0.44

MPC

0.60

ClinPred

0.013

GERP RS

0.71

Varity_R

0.11

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over