dbSNP rs705837: PRSS12:c.1631+3651G>A (chr4-118304785-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_003619.4(PRSS12):c.1631+3651G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.288 in 151,724 control chromosomes in the GnomAD database, including 8,012 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.29 ( 8012 hom., cov: 32)

Consequence

PRSS12
NM_003619.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0640

Publications

6 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: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.73).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.397 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
PRSS12	NM_003619.4 link	c.1631+3651G>A	intron_variant	Intron 8 of 12	ENST00000296498.3	NP_003610.2	P56730Q96I80
PRSS12	NM_001440549.1 link	c.1631+3651G>A	intron_variant	Intron 8 of 12		NP_001427478.1
PRSS12	NM_001440550.1 link	c.1632-906G>A	intron_variant	Intron 8 of 8		NP_001427479.1
PRSS12	NM_001440551.1 link	c.*23-906G>A	intron_variant	Intron 9 of 9		NP_001427480.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRSS12	ENST00000296498.3 link	c.1631+3651G>A		intron_variant	Intron 8 of 12	1	NM_003619.4	ENSP00000296498.3		P56730
PRSS12	ENST00000515089.1 link	n.278-906G>A		intron_variant	Intron 3 of 3	2

Frequencies

GnomAD3 genomes

AF:

0.289

AC:

43746

AN:

151604

Hom.:

8016

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0731

Gnomad AMI

AF:

0.464

Gnomad AMR

AF:

0.371

Gnomad ASJ

AF:

0.392

Gnomad EAS

AF:

0.131

Gnomad SAS

AF:

0.345

Gnomad FIN

AF:

0.283

Gnomad MID

AF:

0.445

Gnomad NFE

AF:

0.401

Gnomad OTH

AF:

0.312

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.288

AC:

43741

AN:

151724

Hom.:

8012

Cov.:

AF XY:

0.285

AC XY:

21154

AN XY:

74140

show subpopulations

African (AFR)

AF:

0.0729

AC:

3022

AN:

41478

American (AMR)

AF:

0.372

AC:

5663

AN:

15242

Ashkenazi Jewish (ASJ)

AF:

0.392

AC:

1359

AN:

3464

East Asian (EAS)

AF:

0.132

AC:

682

AN:

5168

South Asian (SAS)

AF:

0.344

AC:

1655

AN:

4810

European-Finnish (FIN)

AF:

0.283

AC:

2985

AN:

10550

Middle Eastern (MID)

AF:

0.428

AC:

125

AN:

292

European-Non Finnish (NFE)

AF:

0.401

AC:

27175

AN:

67706

Other (OTH)

AF:

0.311

AC:

654

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1419

2838

4256

5675

7094

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

444

888

1332

1776

2220

<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:

0.354

Hom.:

6284

Bravo

AF:

0.282

Asia WGS

AF:

0.233

AC:

813

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

7.3

(source)

DANN

Benign

0.74

PhyloP100

-0.064

Mutation Taster

=100/0

polymorphism (auto)

(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