22-16591521-G-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.710

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 -10 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_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCT8L2	NM_014406.5	c.1030C>A	p.Pro344Thr	missense_variant	1/1	ENST00000359963.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCT8L2	ENST00000359963.4	c.1030C>A	p.Pro344Thr	missense_variant	1/1		NM_014406.5	P1

Frequencies

GnomAD3 genomes AF: 0.00615 AC: 936 AN: 152180 Hom.: 4 Cov.: 33

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.: 6 AF XY: 0.00538 AC XY: 731 AN XY: 135916

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.: 52 Cov.: 30 AF XY: 0.00717 AC XY: 5213 AN XY: 727242

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.: 4 Cov.: 33 AF XY: 0.00630 AC XY: 469 AN XY: 74470

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.: 2

Bravo AF: 0.00534

TwinsUK AF: 0.00755 AC: 28

ALSPAC AF: 0.00960 AC: 37

ESP6500AA AF: 0.000681 AC: 3

ESP6500EA AF: 0.00802 AC: 69

ExAC AF: 0.00509 AC: 618

EpiCase AF: 0.00709

EpiControl AF: 0.00652

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Nov 08, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.45	T
BayesDel_noAF	Benign	-0.41
Cadd	Benign	13
Dann	Benign	0.96
DEOGEN2	Benign	0.092	T
Eigen	Benign	-0.54
Eigen_PC	Benign	-0.66
FATHMM_MKL	Benign	0.011	N
LIST_S2	Benign	0.54	T
MetaRNN	Benign	0.018	T
MetaSVM	Benign	-0.73	T
MutationTaster	Benign	1.0	N
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.18
Sift	Benign	0.33	T
Sift4G	Uncertain	0.022	D
Polyphen		0.45	B
Vest4		0.24
MVP		0.44
MPC		0.60
ClinPred		0.013	T
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

Other links and lift over

dbSNP: rs41277596; hg19: chr22-17072411; COSMIC: COSV99068268; COSMIC: COSV99068268;