rs199996930

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_003619.4(PRSS12):​c.323C>T​(p.Pro108Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000658 in 152,082 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

PRSS12
NM_003619.4 missense

Scores

5
14

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.446
Variant links:
Genes affected
PRSS12 (HGNC:9477): (serine protease 12) This gene encodes a member of the trypsin family of serine proteases and contains a signal peptide, a proline-rich region, a Kringle domain, four scavenger receptor cysteine-rich domains, and a trypsin-like serine protease domain. The protein, sometimes referred to as neurotrypsin or motopsin, is secreted from neuronal cells and localizes to the synaptic cleft. Studies in mice show that this protein cleaves a protein, agrin, that is important for the formation and maintenance of exitatory synapses. Defects in this gene cause a form of autosomal recessive cognitive impairment (MRT1). [provided by RefSeq, Jul 2017]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.18383619).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PRSS12NM_003619.4 linkuse as main transcriptc.323C>T p.Pro108Leu missense_variant 1/13 ENST00000296498.3 NP_003610.2
PRSS12XM_011532387.3 linkuse as main transcriptc.323C>T p.Pro108Leu missense_variant 1/9 XP_011530689.1
PRSS12XM_005263318.5 linkuse as main transcriptc.323C>T p.Pro108Leu missense_variant 1/10 XP_005263375.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PRSS12ENST00000296498.3 linkuse as main transcriptc.323C>T p.Pro108Leu missense_variant 1/131 NM_003619.4 ENSP00000296498 P1

Frequencies

GnomAD3 genomes
AF:
0.00000658
AC:
1
AN:
152082
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1389832
Hom.:
0
Cov.:
30
AF XY:
0.00
AC XY:
0
AN XY:
685962
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:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000658
AC:
1
AN:
152082
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74294
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
ExAC
AF:
0.00000928
AC:
1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.11
BayesDel_addAF
Benign
-0.13
T
BayesDel_noAF
Benign
-0.42
CADD
Benign
20
DANN
Uncertain
1.0
DEOGEN2
Benign
0.090
T
Eigen
Benign
-0.44
Eigen_PC
Benign
-0.48
FATHMM_MKL
Benign
0.36
N
LIST_S2
Benign
0.57
T
M_CAP
Uncertain
0.12
D
MetaRNN
Benign
0.18
T
MetaSVM
Benign
-0.73
T
MutationAssessor
Benign
1.7
L
MutationTaster
Benign
0.81
D
PrimateAI
Uncertain
0.68
T
PROVEAN
Benign
-1.2
N
REVEL
Benign
0.13
Sift
Uncertain
0.025
D
Sift4G
Uncertain
0.035
D
Polyphen
0.71
P
Vest4
0.26
MutPred
0.62
Loss of catalytic residue at P108 (P = 0.0191);
MVP
0.68
MPC
0.40
ClinPred
0.61
D
GERP RS
2.9
Varity_R
0.044
gMVP
0.29

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs199996930; hg19: chr4-119273553; API