4-151277198-C-T

Variant summary

Our verdict is Likely benign. Variant got -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. 15/21 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

19

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.00200
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]
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -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 id is 3426453.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PRSS48NM_183375.5 linkc.26C>T p.Thr9Met missense_variant Exon 1 of 5 ENST00000455694.7 NP_899231.4 Q7RTY5-2A0A140VJJ1
SH3D19NM_001378122.1 linkc.112+48043G>A intron_variant Intron 1 of 19 ENST00000604030.7 NP_001365051.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PRSS48ENST00000455694.7 linkc.26C>T p.Thr9Met missense_variant Exon 1 of 5 1 NM_183375.5 ENSP00000401328.2 Q7RTY5-2
PRSS48ENST00000441586.2 linkc.26C>T p.Thr9Met missense_variant Exon 1 of 3 1 ENSP00000401420.2 Q7RTY5-3
SH3D19ENST00000604030.7 linkc.112+48043G>A intron_variant Intron 1 of 19 5 NM_001378122.1 ENSP00000488951.1 A0A0U1RQE4

Frequencies

GnomAD3 genomes
AF:
0.0000526
AC:
8
AN:
152172
Hom.:
0
Cov.:
32
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
GnomAD3 exomes
AF:
0.0000140
AC:
3
AN:
213586
Hom.:
0
AF XY:
0.0000171
AC XY:
2
AN XY:
116734
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 SAS 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:
92
AN:
1349152
Hom.:
0
Cov.:
30
AF XY:
0.0000613
AC XY:
41
AN XY:
668930
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000572
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000746
Gnomad4 OTH exome
AF:
0.000220
GnomAD4 genome
AF:
0.0000526
AC:
8
AN:
152172
Hom.:
0
Cov.:
32
AF XY:
0.0000538
AC XY:
4
AN XY:
74332
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000118
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000529
ExAC
AF:
0.0000330
AC:
4

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Aug 12, 2024
Ambry Genetics
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.11
BayesDel_addAF
Benign
-0.10
T
BayesDel_noAF
Benign
-0.39
CADD
Benign
0.98
DANN
Benign
0.57
DEOGEN2
Benign
0.0079
T;.
Eigen
Benign
-1.5
Eigen_PC
Benign
-1.5
FATHMM_MKL
Benign
0.0033
N
LIST_S2
Benign
0.31
T;T
M_CAP
Benign
0.017
T
MetaRNN
Benign
0.051
T;T
MetaSVM
Benign
-0.43
T
MutationAssessor
Benign
0.18
N;N
PrimateAI
Benign
0.36
T
PROVEAN
Benign
0.86
N;N
REVEL
Benign
0.12
Sift
Benign
0.16
T;D
Sift4G
Benign
0.14
T;D
Polyphen
0.0
B;B
Vest4
0.16
MVP
0.28
MPC
0.21
ClinPred
0.057
T
GERP RS
1.4
Varity_R
0.012
gMVP
0.33

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.

Other links and lift over

dbSNP: rs747003883; hg19: chr4-152198350; API