rs141401694

Variant names:

• chr22-16591126-G-T
• rs141401694
• NM_014406.5:c.1425C>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_014406.5(CCT8L2):​c.1425C>A​(p.Asn475Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000457 in 1,613,884 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N475T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00030 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00047 (1 hom.)
• Consequence: CCT8L2 NM_014406.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.577
• Publications: 2 publications found

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]

ENSG00000290416 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.064073116).

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.1425C>A	p.Asn475Lys	missense	Exon 1 of 1	NP_055221.1	Q96SF2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCT8L2	ENST00000359963.4	TSL:6 MANE Select	c.1425C>A	p.Asn475Lys	missense	Exon 1 of 1	ENSP00000353048.3	Q96SF2
	ENSG00000290416	ENST00000472972.2	TSL:2	n.287-6432C>A		intron	N/A
	ENSG00000290416	ENST00000725389.1		n.112-6432C>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.000302 AC: 46 AN: 152216 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000851

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000382

Gnomad OTH AF: 0.000958

GnomAD2 exomes AF: 0.000311 AC: 78 AN: 251178 AF XY: 0.000287

Gnomad AFR exome AF: 0.000123

Gnomad AMR exome AF: 0.000896

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000388

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.000473 AC: 691 AN: 1461668 Hom.: 1 Cov.: 30 AF XY: 0.000443 AC XY: 322 AN XY: 727144

African (AFR) AF: 0.0000299 AC: 1 AN: 33472

American (AMR) AF: 0.000895 AC: 40 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86248

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.000558 AC: 620 AN: 1111840

Other (OTH) AF: 0.000497 AC: 30 AN: 60378

GnomAD4 genome AF: 0.000302 AC: 46 AN: 152216 Hom.: 0 Cov.: 33 AF XY: 0.000256 AC XY: 19 AN XY: 74358

African (AFR) AF: 0.000121 AC: 5 AN: 41456

American (AMR) AF: 0.000851 AC: 13 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000382 AC: 26 AN: 68044

Other (OTH) AF: 0.000958 AC: 2 AN: 2088

Alfa AF: 0.000537 Hom.: 0

Bravo AF: 0.000329

TwinsUK AF: 0.00108 AC: 4

ALSPAC AF: 0.00130 AC: 5

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000465 AC: 4

ExAC AF: 0.000231 AC: 28

EpiCase AF: 0.000600

EpiControl AF: 0.000178

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.30
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.17	T
Eigen	Benign	-0.74
Eigen_PC	Benign	-0.78
FATHMM_MKL	Benign	0.029	N
LIST_S2	Benign	0.48	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.064	T
MetaSVM	Benign	-0.61	T
PhyloP100		0.58
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.24
Sift	Benign	0.21	T
Sift4G	Uncertain	0.018	D
Polyphen		0.045	B
Vest4		0.34
MutPred		0.66		Gain of ubiquitination at N475 (P = 0.0219)
MVP		0.24
MPC		0.47
ClinPred		0.028	T
GERP RS		2.0
Varity_R		0.16
gMVP		0.14
Mutation Taster		=95/5	polymorphism

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

Other links and lift over

dbSNP: rs141401694; hg19: chr22-17072016;