rs748610072

Variant names:

• chr2-44339257-C-A
• NM_001171613.2:c.592G>T

Your query was ambiguous. Multiple possible variants found:

• chr2-44339257-C-A
• chr2-44339257-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001171613.2(PREPL):​c.592G>T​(p.Asp198Tyr) 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 1,461,820 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. D198N) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: PREPL NM_001171613.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.85

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.747

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PREPL	NM_001171613.2	c.592G>T	p.Asp198Tyr	missense_variant	Exon 6 of 14	ENST00000409411.6	NP_001165084.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PREPL	ENST00000409411.6	c.592G>T	p.Asp198Tyr	missense_variant	Exon 6 of 14	1	NM_001171613.2	ENSP00000387095.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461820 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727204

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: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.053	T
BayesDel_noAF	Benign	-0.31
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.061	.;.;.;T;T;T;T;.;.
Eigen	Uncertain	0.42
Eigen_PC	Uncertain	0.46
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Uncertain	0.91	D;.;.;.;.;.;D;D;D
M_CAP	Benign	0.018	T
MetaRNN	Pathogenic	0.75	D;D;D;D;D;D;D;D;D
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	0.34	.;.;.;N;N;N;N;N;N
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-2.2	N;N;N;N;N;N;N;N;N
REVEL	Benign	0.18
Sift	Uncertain	0.010	D;D;D;D;D;D;D;D;D
Sift4G	Uncertain	0.026	D;D;D;D;D;D;D;D;D
Polyphen		0.82, 0.99, 1.0	.;.;.;P;P;P;P;D;D
Vest4		0.64
MutPred		0.56		.;.;.;Loss of sheet (P = 0.0357);Loss of sheet (P = 0.0357);Loss of sheet (P = 0.0357);Loss of sheet (P = 0.0357);Loss of sheet (P = 0.0357);Loss of sheet (P = 0.0357);
MVP		0.59
MPC		0.0074
ClinPred		0.91	D
GERP RS		4.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.23
gMVP		0.55

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: chr2-44566396;