4-151279861-C-A

Variant names:

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_183375.5(PRSS48):c.118C>A(p.Pro40Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000945 in 1,375,362 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000095 ( 0 hom. )

Consequence

PRSS48
NM_183375.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.32

Publications

2 publications found

Variant links:

Genes affected

PRSS48 (HGNC:24635): (serine protease 48) Predicted to enable serine-type endopeptidase activity. Predicted to be involved in proteolysis. Predicted to be active in extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

PRSS48 links:

SH3D19 (HGNC:30418): (SH3 domain containing 19) This gene encodes a multiple SH3 domain-containing protein, which interacts with other proteins, such as EBP and members of ADAM family, via the SH3 domains. This protein may be involved in suppression of Ras-induced cellular transformation and Ras-mediated activation of ELK1 by EBP, and regulation of ADAM proteins in the signaling of EGFR-ligand shedding. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2011]

SH3D19 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.981

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_183375.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PRSS48	NM_183375.5	MANE Select	c.118C>A	p.Pro40Thr	missense	Exon 2 of 5	NP_899231.4	Q7RTY5-2
SH3D19	NM_001378122.1	MANE Select	c.112+45380G>T		intron	N/A	NP_001365051.1	A0A0U1RQE4
SH3D19	NM_001378121.1		c.112+45380G>T		intron	N/A	NP_001365050.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PRSS48	ENST00000455694.7	TSL:1 MANE Select	c.118C>A	p.Pro40Thr	missense	Exon 2 of 5	ENSP00000401328.2	Q7RTY5-2
SH3D19	ENST00000604030.7	TSL:5 MANE Select	c.112+45380G>T		intron	N/A	ENSP00000488951.1	A0A0U1RQE4
PRSS48	ENST00000441586.2	TSL:1	c.52+2637C>A		intron	N/A	ENSP00000401420.2	Q7RTY5-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000364

AC:

AN:

219600

AF XY:

0.0000507

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000582

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000945

AC:

AN:

1375362

Hom.:

Cov.:

AF XY:

0.0000146

AC XY:

AN XY:

686994

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33112

American (AMR)

AF:

0.00

AC:

AN:

44438

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25732

East Asian (EAS)

AF:

0.00

AC:

AN:

39516

South Asian (SAS)

AF:

0.000129

AC:

AN:

85276

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52688

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5426

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1031478

Other (OTH)

AF:

0.0000347

AC:

AN:

57696

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.444

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000496

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.56

BayesDel_addAF

Uncertain

0.083

BayesDel_noAF

Pathogenic

0.17

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.59

Eigen

Pathogenic

0.87

Eigen_PC

Pathogenic

0.74

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.92

M_CAP

Benign

0.050

MetaRNN

Pathogenic

0.98

MetaSVM

Uncertain

0.56

MutationAssessor

Pathogenic

3.6

PhyloP100

7.3

PrimateAI

Benign

0.43

PROVEAN

Pathogenic

-7.8

REVEL

Pathogenic

0.66

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.80

MutPred

0.95

Loss of glycosylation at P40 (P = 0.1855)

MVP

0.92

MPC

0.83

ClinPred

0.99

GERP RS

4.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Varity_R

0.88

gMVP

0.99

Mutation Taster

=32/68

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.18

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over