4-151277198-C-T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_183375.5(PRSS48):c.26C>T(p.Thr9Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000666 in 1,501,324 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000068 ( 0 hom. )

Consequence

PRSS48
NM_183375.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.00200

Publications

0 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.05120042).

BP6

Variant 4-151277198-C-T is Benign according to our data. Variant chr4-151277198-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3426453.Status of the report is criteria_provided_single_submitter, 1 stars.

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.26C>T	p.Thr9Met	missense	Exon 1 of 5	NP_899231.4	Q7RTY5-2
SH3D19	NM_001378122.1	MANE Select	c.112+48043G>A		intron	N/A	NP_001365051.1	A0A0U1RQE4
SH3D19	NM_001378121.1		c.112+48043G>A		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.26C>T	p.Thr9Met	missense	Exon 1 of 5	ENSP00000401328.2	Q7RTY5-2
PRSS48	ENST00000441586.2	TSL:1	c.26C>T	p.Thr9Met	missense	Exon 1 of 3	ENSP00000401420.2	Q7RTY5-3
SH3D19	ENST00000604030.7	TSL:5 MANE Select	c.112+48043G>A		intron	N/A	ENSP00000488951.1	A0A0U1RQE4

Frequencies

GnomAD3 genomes

AF:

0.0000526

AC:

AN:

152172

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:

0.000118

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000140

AC:

AN:

213586

AF XY:

0.0000171

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000300

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000682

AC:

AN:

1349152

Hom.:

Cov.:

AF XY:

0.0000613

AC XY:

AN XY:

668930

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30464

American (AMR)

AF:

0.00

AC:

AN:

38992

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23412

East Asian (EAS)

AF:

0.0000572

AC:

AN:

34950

South Asian (SAS)

AF:

0.00

AC:

AN:

70078

European-Finnish (FIN)

AF:

0.00

AC:

AN:

46376

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5264

European-Non Finnish (NFE)

AF:

0.0000746

AC:

AN:

1045056

Other (OTH)

AF:

0.000220

AC:

AN:

54560

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

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

AF:

0.0000526

AC:

AN:

152172

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74332

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41426

American (AMR)

AF:

0.00

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000118

AC:

AN:

68044

Other (OTH)

AF:

0.00

AC:

AN:

2086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

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:

0.00

Hom.:

Bravo

AF:

0.0000529

ExAC

AF:

0.0000330

AC:

ClinVar

ClinVar submissions

Significance:Likely benign

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

Benign

0.11

BayesDel_addAF

Benign

-0.10

BayesDel_noAF

Benign

-0.39

CADD

Benign

0.98

(source)

DANN

Benign

0.57

DEOGEN2

Benign

0.0079

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.0033

LIST_S2

Benign

0.31

M_CAP

Benign

0.017

MetaRNN

Benign

0.051

MetaSVM

Benign

-0.43

MutationAssessor

Benign

0.18

PhyloP100

-0.0020

PrimateAI

Benign

0.36

PROVEAN

Benign

0.86

REVEL

Benign

0.12

Sift

Benign

0.16

Sift4G

Benign

0.14

Polyphen

0.0

Vest4

0.16

MVP

0.28

MPC

0.21

ClinPred

0.057

GERP RS

1.4

PromoterAI

0.00090

Neutral

(source)

Varity_R

0.012

gMVP

0.33

Mutation Taster

=97/3

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over