Variant 7-141837940-G-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001008270.3(PRSS37):c.350C>A(p.Pro117His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000229 in 1,613,998 control chromosomes in the GnomAD database, with no homozygous occurrence. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000024 ( 0 hom. )

Consequence

PRSS37
NM_001008270.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.32

Variant links:

Genes affected

PRSS37 (HGNC:29211): (serine protease 37) Predicted to enable serine-type endopeptidase activity. Involved in positive regulation of acrosome reaction and regulation of protein processing. Located in acrosomal vesicle. [provided by Alliance of Genome Resources, Apr 2022]

PRSS37 links:

Genome browser will be placed here

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	UniProt
PRSS37	NM_001008270.3 linkuse as main transcript	c.350C>A	p.Pro117His	missense_variant	3/5	ENST00000350549.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
PRSS37	ENST00000350549.8 linkuse as main transcript	c.350C>A	p.Pro117His	missense_variant	3/5	1	NM_001008270.3	P1
PRSS37	ENST00000452758.1 linkuse as main transcript	c.*120C>A		3_prime_UTR_variant, NMD_transcript_variant	3/5	1
PRSS37	ENST00000438520.1 linkuse as main transcript	c.350C>A	p.Pro117His	missense_variant	4/6	5		P1
PRSS37	ENST00000419085.5 linkuse as main transcript	c.*1034C>A		3_prime_UTR_variant, NMD_transcript_variant	4/7	2

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152116

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000199

AC:

AN:

251480

Hom.:

AF XY:

0.0000221

AC XY:

AN XY:

135910

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:

0.0000440

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000239

AC:

AN:

1461882

Hom.:

Cov.:

AF XY:

0.0000275

AC XY:

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000315

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152116

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74292

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:

0.0000294

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ExAC

AF:

0.0000165

AC:

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

Mar 13, 2023

The c.350C>A (p.P117H) alteration is located in exon 3 (coding exon 3) of the PRSS37 gene. This alteration results from a C to A substitution at nucleotide position 350, causing the proline (P) at amino acid position 117 to be replaced by a histidine (H). 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

Uncertain

0.42

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.32

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Uncertain

0.66

D;D

Eigen

Benign

-0.78

Eigen_PC

Benign

-0.89

FATHMM_MKL

Benign

0.34

M_CAP

Benign

0.039

MetaRNN

Uncertain

0.50

T;T

MetaSVM

Benign

-0.78

MutationAssessor

Pathogenic

2.9

M;M

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.33

PROVEAN

Uncertain

-2.6

D;D

REVEL

Benign

0.23

Sift

Uncertain

0.014

D;D

Sift4G

Uncertain

0.052

T;T

Polyphen

0.053

B;B

Vest4

0.47

MutPred

0.67

Gain of sheet (P = 0.0827);Gain of sheet (P = 0.0827);

MVP

0.35

MPC

0.50

ClinPred

0.21

GERP RS

-1.5

Varity_R

0.30

gMVP

0.62

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