Variant rs373311928 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 2P and 13B. PM2BP4_StrongBP6_Very_StrongBP7

The NM_003619.4(PRSS12):c.309G>C(p.Thr103Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000468 in 1,534,716 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0025 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00024 ( 1 hom. )

Consequence

PRSS12
NM_003619.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.43

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.63).

BP6

Variant 4-118352412-C-G is Benign according to our data. Variant chr4-118352412-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 211962.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.43 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRSS12	NM_003619.4 link	c.309G>C	p.Thr103Thr	synonymous_variant	1/13	ENST00000296498.3	NP_003610.2	P56730Q96I80
PRSS12	XM_011532387.3 link	c.309G>C	p.Thr103Thr	synonymous_variant	1/9		XP_011530689.1
PRSS12	XM_005263318.5 link	c.309G>C	p.Thr103Thr	synonymous_variant	1/10		XP_005263375.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRSS12	ENST00000296498.3 link	c.309G>C	p.Thr103Thr	synonymous_variant	1/13	1	NM_003619.4	ENSP00000296498.3		P56730

Frequencies

GnomAD3 genomes

AF:

0.00245

AC:

373

AN:

152026

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00871

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000589

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:

0.00

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.000517

AC:

AN:

129688

Hom.:

AF XY:

0.000478

AC XY:

AN XY:

71194

show subpopulations

Gnomad AFR exome

AF:

0.00936

Gnomad AMR exome

AF:

0.000388

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000261

GnomAD4 exome

AF:

0.000242

AC:

335

AN:

1382578

Hom.:

Cov.:

AF XY:

0.000202

AC XY:

138

AN XY:

681854

show subpopulations

Gnomad4 AFR exome

AF:

0.00907

Gnomad4 AMR exome

AF:

0.000484

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:

9.29e-7

Gnomad4 OTH exome

AF:

0.000538

GnomAD4 genome

AF:

0.00252

AC:

383

AN:

152138

Hom.:

Cov.:

AF XY:

0.00247

AC XY:

184

AN XY:

74372

show subpopulations

Gnomad4 AFR

AF:

0.00893

Gnomad4 AMR

AF:

0.000589

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000907

Hom.:

Bravo

AF:

0.00294

Asia WGS

AF:

0.00202

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Dec 17, 2018

- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.63

CADD

Benign

5.8

DANN

Benign

0.75

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over