rs41277596

Variant names:

• chr22-16591521-G-C
• NM_014406.5:c.1030C>G

Your query was ambiguous. Multiple possible variants found:

• chr22-16591521-G-C
• chr22-16591521-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014406.5(CCT8L2):​c.1030C>G​(p.Pro344Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,888 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P344T) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CCT8L2 NM_014406.5 missense
• Clinical Significance: Not reported in ClinVar
• 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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1875794).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCT8L2	NM_014406.5	c.1030C>G	p.Pro344Ala	missense_variant	Exon 1 of 1	ENST00000359963.4	NP_055221.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCT8L2	ENST00000359963.4	c.1030C>G	p.Pro344Ala	missense_variant	Exon 1 of 1	6	NM_014406.5	ENSP00000353048.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461888 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 727248

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	11
DANN	Benign	0.50
DEOGEN2	Benign	0.092	T
Eigen	Benign	-0.84
Eigen_PC	Benign	-0.87
FATHMM_MKL	Benign	0.014	N
LIST_S2	Benign	0.48	T
M_CAP	Benign	0.0088	T
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-0.83	T
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-0.82	N
REVEL	Benign	0.13
Sift	Benign	0.47	T
Sift4G	Benign	0.23	T
Polyphen		0.012	B
Vest4		0.15
MutPred		0.49		Gain of catalytic residue at P344 (P = 0.0146);
MVP		0.32
MPC		0.20
ClinPred		0.10	T
GERP RS		0.71
Varity_R		0.072
gMVP		0.16

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr22-17072411;