chr5-64769178-C-T

Variant names:

• chr5-64769178-C-T
• rs529010023
• NM_005869.4:c.32C>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_005869.4(CWC27):​c.32C>T​(p.Thr11Met) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,790 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. T11T) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: CWC27 NM_005869.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.84
• Publications: 1 publications found

Genes affected

CWC27 (HGNC:10664): (CWC27 spliceosome associated cyclophilin) Predicted to enable peptidyl-prolyl cis-trans isomerase activity. Predicted to be involved in protein peptidyl-prolyl isomerization. Located in nucleoplasm. Part of U2-type precatalytic spliceosome and catalytic step 2 spliceosome. [provided by Alliance of Genome Resources, Apr 2022]

CWC27 Gene-Disease associations (from GenCC):

• metaphyseal chondrodysplasia-retinitis pigmentosa syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005869.4. 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
	CWC27	NM_005869.4	MANE Select	c.32C>T	p.Thr11Met	missense	Exon 1 of 14	NP_005860.2	Q6UX04-1
	CWC27	NM_001297644.1		c.32C>T	p.Thr11Met	missense	Exon 1 of 13	NP_001284573.1	Q6UX04
	CWC27	NM_001297645.2		c.32C>T	p.Thr11Met	missense	Exon 1 of 11	NP_001284574.1	D6REK3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CWC27	ENST00000381070.8	TSL:1 MANE Select	c.32C>T	p.Thr11Met	missense	Exon 1 of 14	ENSP00000370460.2	Q6UX04-1
	CWC27	ENST00000508024.2	TSL:1	c.32C>T	p.Thr11Met	missense	Exon 1 of 11	ENSP00000426802.1	D6REK3
	CWC27	ENST00000693660.1		c.32C>T	p.Thr11Met	missense	Exon 1 of 13	ENSP00000509052.1	A0A8I5KST0

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461790 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727184

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5744

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111940

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.87
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.070
CADD	Pathogenic	32
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.29	T
Eigen	Pathogenic	0.77
Eigen_PC	Pathogenic	0.69
FATHMM_MKL	Uncertain	0.76	D
LIST_S2	Pathogenic	0.99	D
M_CAP	Benign	0.036	D
MetaRNN	Uncertain	0.54	D
MetaSVM	Benign	-0.51	T
MutationAssessor	Pathogenic	3.1	M
PhyloP100		6.8
PrimateAI	Pathogenic	0.80	D
PROVEAN	Pathogenic	-5.0	D
REVEL	Uncertain	0.34
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0010	D
Polyphen		1.0	D
Vest4		0.60
MutPred		0.35		Loss of relative solvent accessibility (P = 0.0676)
MVP		0.51
MPC		0.23
ClinPred		1.0	D
GERP RS		4.4
PromoterAI		-0.043	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.76
gMVP		0.77
Mutation Taster		=30/70	disease causing

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: rs529010023; hg19: chr5-64065005;