11-94972079-G-A

Position:

• chr11-94972079-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_016403.4(CWC15):​c.107C>T​(p.Pro36Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CWC15 NM_016403.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.08

Genes affected

CWC15 (HGNC:26939): (CWC15 spliceosome associated protein homolog) Predicted to enable RNA binding activity. Involved in mRNA splicing, via spliceosome. Located in mitochondrion and nuclear speck. Part of U2-type catalytic step 2 spliceosome. [provided by Alliance of Genome Resources, Apr 2022]

CWC15 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.904

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CWC15	NM_016403.4	c.107C>T	p.Pro36Leu	missense_variant	2/7	ENST00000279839.8	NP_057487.2
CWC15	NM_001363371.2	c.107C>T	p.Pro36Leu	missense_variant	2/7		NP_001350300.1
CWC15	NM_001363372.2	c.107C>T	p.Pro36Leu	missense_variant	2/7		NP_001350301.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CWC15	ENST00000279839.8	c.107C>T	p.Pro36Leu	missense_variant	2/7	1	NM_016403.4	ENSP00000475615.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 21, 2023

The c.107C>T (p.P36L) alteration is located in exon 2 (coding exon 1) of the CWC15 gene. This alteration results from a C to T substitution at nucleotide position 107, causing the proline (P) at amino acid position 36 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Pathogenic	0.59	D
BayesDel_noAF	Pathogenic	0.62
CADD	Pathogenic	31
DANN	Benign	0.91
DEOGEN2	Benign	0.37	T
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Uncertain	0.19	D
MetaRNN	Pathogenic	0.90	D
PrimateAI	Pathogenic	0.86	D
Sift4G	Uncertain	0.0050	D
Polyphen		1.0	D
Vest4		0.91
MVP		0.93
MPC		2.2
GERP RS		6.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.38
gMVP		0.83

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-94705243;