Variant chr6-83523872-T-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_153362.3(PRSS35):c.431T>A(p.Phe144Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00019 in 1,614,104 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00020 ( 0 hom. )

Consequence

PRSS35
NM_153362.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.67

Variant links:

Genes affected

PRSS35 (HGNC:21387): (serine protease 35) Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

PRSS35 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	Protein	UniProt
PRSS35	NM_153362.3 linkuse as main transcript	c.431T>A	p.Phe144Tyr	missense_variant	2/2	ENST00000369700.4	NP_699193.2	Q8N3Z0
PRSS35	NM_001170423.2 linkuse as main transcript	c.431T>A	p.Phe144Tyr	missense_variant	3/3		NP_001163894.1	Q8N3Z0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRSS35	ENST00000369700.4 linkuse as main transcript	c.431T>A	p.Phe144Tyr	missense_variant	2/2	1	NM_153362.3	ENSP00000358714.3		Q8N3Z0

Frequencies

GnomAD3 genomes

AF:

0.000131

AC:

AN:

152210

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

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:

0.000162

Gnomad OTH

AF:

0.000957

GnomAD3 exomes

AF:

0.000299

AC:

AN:

251080

Hom.:

AF XY:

0.000265

AC XY:

AN XY:

135662

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.000839

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000277

Gnomad NFE exome

AF:

0.000317

Gnomad OTH exome

AF:

0.000489

GnomAD4 exome

AF:

0.000196

AC:

287

AN:

1461894

Hom.:

Cov.:

AF XY:

0.000195

AC XY:

142

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.000805

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000112

Gnomad4 NFE exome

AF:

0.000208

Gnomad4 OTH exome

AF:

0.000215

GnomAD4 genome

AF:

0.000131

AC:

AN:

152210

Hom.:

Cov.:

AF XY:

0.0000673

AC XY:

AN XY:

74346

show subpopulations

Gnomad4 AFR

AF:

0.0000482

Gnomad4 AMR

AF:

0.000327

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000162

Gnomad4 OTH

AF:

0.000957

Alfa

AF:

0.000200

Hom.:

Bravo

AF:

0.000219

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000362

AC:

EpiCase

AF:

0.000164

EpiControl

AF:

0.000119

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

Apr 13, 2023

The c.431T>A (p.F144Y) alteration is located in exon 3 (coding exon 1) of the PRSS35 gene. This alteration results from a T to A substitution at nucleotide position 431, causing the phenylalanine (F) at amino acid position 144 to be replaced by a tyrosine (Y). 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

0.81

BayesDel_addAF

Benign

0.0043

BayesDel_noAF

Pathogenic

0.15

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.41

Eigen

Uncertain

0.45

Eigen_PC

Uncertain

0.47

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.95

M_CAP

Uncertain

0.10

MetaRNN

Uncertain

0.65

MetaSVM

Uncertain

0.36

MutationAssessor

Benign

0.79

PrimateAI

Uncertain

0.65

PROVEAN

Uncertain

-2.4

REVEL

Pathogenic

0.71

Sift

Pathogenic

0.0

Sift4G

Benign

0.079

Polyphen

1.0

Vest4

0.72

MVP

0.30

ClinPred

0.10

GERP RS

5.8

Varity_R

0.67

gMVP

0.76

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