Genetic Variant CCT8L2:p.Pro344Thr (chr22-16591521-G-T) – ACMG Classification: Benign (-16 pts)

Variant summary

Our verdict is Benign. The variant received -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. 14/20 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

Publications

7 publications found

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:

ENSG00000290416 (HGNC:):

ENSG00000290416 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 782172.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCT8L2	NM_014406.5	MANE Select	c.1030C>A	p.Pro344Thr	missense	Exon 1 of 1	NP_055221.1	Q96SF2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CCT8L2	ENST00000359963.4	TSL:6 MANE Select	c.1030C>A	p.Pro344Thr	missense	Exon 1 of 1	ENSP00000353048.3	Q96SF2
ENSG00000290416	ENST00000472972.2	TSL:2	n.287-6827C>A		intron	N/A
ENSG00000290416	ENST00000725389.1		n.112-6827C>A		intron	N/A

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

GnomAD2 exomes

AF:

0.00535

AC:

1346

AN:

251456

AF XY:

0.00538

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 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

African (AFR)

AF:

0.000717

AC:

AN:

33478

American (AMR)

AF:

0.00233

AC:

104

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00138

AC:

AN:

26136

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39700

South Asian (SAS)

AF:

0.00202

AC:

174

AN:

86256

European-Finnish (FIN)

AF:

0.0132

AC:

707

AN:

53418

Middle Eastern (MID)

AF:

0.00433

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00824

AC:

9161

AN:

1112008

Other (OTH)

AF:

0.00700

AC:

423

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

712

1424

2135

2847

3559

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

336

672

1008

1344

1680

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00614

AC:

935

AN:

152298

Hom.:

Cov.:

AF XY:

0.00630

AC XY:

469

AN XY:

74470

show subpopulations

African (AFR)

AF:

0.00164

AC:

AN:

41574

American (AMR)

AF:

0.00621

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00202

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5170

South Asian (SAS)

AF:

0.00124

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.0148

AC:

157

AN:

10614

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00863

AC:

587

AN:

68024

Other (OTH)

AF:

0.00567

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

140

187

234

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00711

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

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.41

CADD

Benign

(source)

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

PhyloP100

0.71

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

Mutation Taster

=93/7

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over