Variant 1-227816092-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_183062.3(PRSS38):c.151T>G(p.Cys51Gly) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000659 in 151,694 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. C51Y) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)

Consequence

PRSS38
NM_183062.3 missense, splice_region

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0990

Variant links:

Genes affected

PRSS38 (HGNC:29625): (serine protease 38) Predicted to enable serine-type endopeptidase activity. Predicted to be involved in proteolysis. Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

PRSS38 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRSS38	NM_183062.3 linkuse as main transcript	c.151T>G	p.Cys51Gly	missense_variant, splice_region_variant	2/5	ENST00000366757.4	NP_898885.1	A1L453
PRSS38	NM_001374657.2 linkuse as main transcript	c.151T>G	p.Cys51Gly	missense_variant, splice_region_variant	2/4		NP_001361586.1
PRSS38	XM_011544175.3 linkuse as main transcript	c.151T>G	p.Cys51Gly	missense_variant, splice_region_variant	2/5		XP_011542477.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRSS38	ENST00000366757.4 linkuse as main transcript	c.151T>G	p.Cys51Gly	missense_variant, splice_region_variant	2/5	1	NM_183062.3	ENSP00000355719.3		A1L453

Frequencies

GnomAD3 genomes

AF:

0.00000659

AC:

AN:

151694

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000659

AC:

AN:

151694

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74136

show subpopulations

Gnomad4 AFR

AF:

0.0000242

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:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 22, 2023

The c.151T>G (p.C51G) alteration is located in exon 2 (coding exon 2) of the PRSS38 gene. This alteration results from a T to G substitution at nucleotide position 151, causing the cysteine (C) at amino acid position 51 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.64

BayesDel_addAF

Uncertain

0.063

BayesDel_noAF

Benign

-0.15

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.12

Eigen

Benign

-0.020

Eigen_PC

Benign

-0.15

FATHMM_MKL

Benign

0.69

LIST_S2

Benign

0.35

M_CAP

Benign

0.024

MetaRNN

Uncertain

0.53

MetaSVM

Benign

-0.39

MutationAssessor

Benign

0.97

PrimateAI

Benign

0.46

PROVEAN

Pathogenic

-9.6

REVEL

Uncertain

0.36

Sift

Uncertain

0.0090

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.26

MutPred

0.69

Gain of disorder (P = 0.0019);

MVP

0.75

MPC

0.40

ClinPred

1.0

GERP RS

2.9

Varity_R

0.62

gMVP

0.58

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