Genetic Variant PRSS12:p.Thr685Ser (chr4-118283097-G-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_003619.4(PRSS12):c.2054C>G(p.Thr685Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. T685I) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

PRSS12
NM_003619.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.53

Publications

2 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 links:

SNHG8 (HGNC:33098): (small nucleolar RNA host gene 8)

SNHG8 links:

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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=0.23483801).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003619.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRSS12	NM_003619.4	MANE Select	c.2054C>G	p.Thr685Ser	missense	Exon 12 of 13	NP_003610.2
	PRSS12	NM_001440549.1		c.2054C>G	p.Thr685Ser	missense	Exon 12 of 13	NP_001427478.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
PRSS12	ENST00000296498.3	TSL:1 MANE Select	c.2054C>G	p.Thr685Ser	missense	Exon 12 of 13	ENSP00000296498.3
PRSS12	ENST00000510903.1	TSL:5	n.137C>G		non_coding_transcript_exon	Exon 3 of 3
SNHG8	ENST00000654083.3		n.4132G>C		non_coding_transcript_exon	Exon 3 of 3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

251418

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1461812

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727208

African (AFR)

AF:

0.00

AC:

AN:

33476

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53404

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111958

Other (OTH)

AF:

0.00

AC:

AN:

60392

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000164

Hom.:

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.096

BayesDel_addAF

Benign

-0.0070

BayesDel_noAF

Benign

-0.25

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.14

Eigen

Benign

-0.20

Eigen_PC

Benign

-0.030

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.64

M_CAP

Benign

0.030

MetaRNN

Benign

0.23

MetaSVM

Benign

-0.33

MutationAssessor

Benign

0.73

PhyloP100

4.5

PrimateAI

Benign

0.42

PROVEAN

Benign

-0.98

REVEL

Uncertain

0.34

Sift

Benign

0.093

Sift4G

Benign

0.33

Polyphen

0.29

Vest4

0.23

MutPred

0.48

Gain of disorder (P = 0.0209)

MVP

0.76

MPC

0.26

ClinPred

0.58

GERP RS

5.9

Varity_R

0.12

gMVP

0.46

Mutation Taster

=70/30

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over