rs148007619

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_003619.4(PRSS12):c.19G>T(p.Val7Leu) 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 152,036 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V7M) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Consequence

PRSS12
NM_003619.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.147

Publications

1 publications found

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]

PRSS12 Gene-Disease associations (from GenCC):

intellectual disability, autosomal recessive 1
Inheritance: Unknown, AR Classification: DEFINITIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P
autosomal recessive non-syndromic intellectual disability
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
non-syndromic intellectual disability
Inheritance: AR Classification: LIMITED Submitted by: Illumina, ClinGen

PRSS12 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.14853588).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
PRSS12	NM_003619.4 link	c.19G>T	p.Val7Leu	missense_variant	Exon 1 of 13	ENST00000296498.3	NP_003610.2
PRSS12	NM_001440549.1 link	c.19G>T	p.Val7Leu	missense_variant	Exon 1 of 13		NP_001427478.1
PRSS12	NM_001440550.1 link	c.19G>T	p.Val7Leu	missense_variant	Exon 1 of 9		NP_001427479.1
PRSS12	NM_001440551.1 link	c.19G>T	p.Val7Leu	missense_variant	Exon 1 of 10		NP_001427480.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRSS12	ENST00000296498.3 link	c.19G>T	p.Val7Leu	missense_variant	Exon 1 of 13	1	NM_003619.4	ENSP00000296498.3

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

152036

Hom.:

Cov.:

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

Cov.:

GnomAD4 genome

AF:

0.00000658

AC:

AN:

152036

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74238

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41428

American (AMR)

AF:

0.00

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5142

South Asian (SAS)

AF:

0.00

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10586

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

67982

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000540

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.065

BayesDel_noAF

Benign

-0.33

CADD

Benign

5.8

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.067

Eigen

Benign

-0.73

Eigen_PC

Benign

-0.69

FATHMM_MKL

Benign

0.20

LIST_S2

Benign

0.49

M_CAP

Pathogenic

0.76

MetaRNN

Benign

0.15

MetaSVM

Benign

-0.59

MutationAssessor

Benign

0.69

PhyloP100

-0.15

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-0.55

REVEL

Benign

0.21

Sift

Benign

0.091

Sift4G

Benign

0.095

Polyphen

0.032

Vest4

0.14

MutPred

0.29

Loss of catalytic residue at V7 (P = 0.004);

MVP

0.46

MPC

0.27

ClinPred

0.49

GERP RS

3.0

PromoterAI

0.043

Neutral

(source)

Varity_R

0.12

gMVP

0.20

Mutation Taster

=92/8

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over