rs150341120

Positions:

• chr2-44339287-C-G
• chr2-44339287-C-T

Variant summary

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

The NM_001171613.2(PREPL):​c.562G>C​(p.Val188Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PREPL NM_001171613.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.43

Genes affected

PREPL (HGNC:30228): (prolyl endopeptidase like) The protein encoded by this gene belongs to the prolyl oligopeptidase subfamily of serine peptidases. Mutations in this gene have been associated with hypotonia-cystinuria syndrome, also known as the 2p21 deletion syndrome. Several alternatively spliced transcript variants encoding either the same or different isoforms have been described for this gene.[provided by RefSeq, Jan 2010]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PREPL	NM_001171613.2	c.562G>C	p.Val188Leu	missense_variant	6/14	ENST00000409411.6	NP_001165084.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PREPL	ENST00000409411.6	c.562G>C	p.Val188Leu	missense_variant	6/14	1	NM_001171613.2	ENSP00000387095.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.79
BayesDel_addAF	Uncertain	0.055	T
BayesDel_noAF	Benign	-0.16
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.059	.;.;.;T;T;T;T;.;.
Eigen	Pathogenic	0.71
Eigen_PC	Pathogenic	0.70
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.93	D;.;.;.;.;.;D;D;D
M_CAP	Benign	0.025	T
MetaRNN	Uncertain	0.72	D;D;D;D;D;D;D;D;D
MetaSVM	Benign	-0.72	T
MutationAssessor	Benign	1.1	.;.;.;L;L;L;L;L;L
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-2.0	N;N;N;N;N;N;N;N;N
REVEL	Benign	0.20
Sift	Benign	0.13	T;T;T;T;T;T;T;T;T
Sift4G	Pathogenic	0.0	D;D;D;D;D;D;D;D;D
Polyphen		1.0, 1.0, 0.96	.;.;.;D;D;D;D;D;D
Vest4		0.76
MutPred		0.51		.;.;.;Gain of ubiquitination at K272 (P = 0.1446);Gain of ubiquitination at K272 (P = 0.1446);Gain of ubiquitination at K272 (P = 0.1446);Gain of ubiquitination at K272 (P = 0.1446);Gain of ubiquitination at K272 (P = 0.1446);Gain of ubiquitination at K272 (P = 0.1446);
MVP		0.71
MPC		0.015
ClinPred		0.96	D
GERP RS		5.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.33
gMVP		0.70

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs150341120; hg19: chr2-44566426;