Genetic Variant PRSS35:p.Ser328Ser (chr6-83524425-C-T) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_153362.3(PRSS35):c.984C>T(p.Ser328Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.164 in 1,613,828 control chromosomes in the GnomAD database, including 23,057 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.18 ( 2691 hom., cov: 32)

Exomes 𝑓: 0.16 ( 20366 hom. )

Consequence

PRSS35
NM_153362.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.34

Publications

12 publications found

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 was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.65).

BP7

Synonymous conserved (PhyloP=-3.34 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.243 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRSS35	NM_153362.3 link	c.984C>T	p.Ser328Ser	synonymous_variant	Exon 2 of 2	ENST00000369700.4	NP_699193.2
PRSS35	NM_001170423.2 link	c.984C>T	p.Ser328Ser	synonymous_variant	Exon 3 of 3		NP_001163894.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRSS35	ENST00000369700.4 link	c.984C>T	p.Ser328Ser	synonymous_variant	Exon 2 of 2	1	NM_153362.3	ENSP00000358714.3

Frequencies

GnomAD3 genomes

AF:

0.180

AC:

27278

AN:

151848

Hom.:

2689

Cov.:

show subpopulations

Gnomad AFR

AF:

0.247

Gnomad AMI

AF:

0.194

Gnomad AMR

AF:

0.121

Gnomad ASJ

AF:

0.160

Gnomad EAS

AF:

0.238

Gnomad SAS

AF:

0.235

Gnomad FIN

AF:

0.144

Gnomad MID

AF:

0.160

Gnomad NFE

AF:

0.150

Gnomad OTH

AF:

0.168

GnomAD2 exomes

AF:

0.168

AC:

42173

AN:

250956

AF XY:

0.173

show subpopulations

Gnomad AFR exome

AF:

0.244

Gnomad AMR exome

AF:

0.0843

Gnomad ASJ exome

AF:

0.166

Gnomad EAS exome

AF:

0.260

Gnomad FIN exome

AF:

0.148

Gnomad NFE exome

AF:

0.154

Gnomad OTH exome

AF:

0.157

GnomAD4 exome

AF:

0.163

AC:

237954

AN:

1461862

Hom.:

20366

Cov.:

AF XY:

0.165

AC XY:

120353

AN XY:

727232

show subpopulations

African (AFR)

AF:

0.251

AC:

8400

AN:

33480

American (AMR)

AF:

0.0877

AC:

3922

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.165

AC:

4304

AN:

26136

East Asian (EAS)

AF:

0.270

AC:

10709

AN:

39700

South Asian (SAS)

AF:

0.238

AC:

20551

AN:

86258

European-Finnish (FIN)

AF:

0.154

AC:

8217

AN:

53412

Middle Eastern (MID)

AF:

0.146

AC:

840

AN:

5768

European-Non Finnish (NFE)

AF:

0.154

AC:

170963

AN:

1111988

Other (OTH)

AF:

0.166

AC:

10048

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

12395

24791

37186

49582

61977

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6238

12476

18714

24952

31190

<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:

0.180

AC:

27282

AN:

151966

Hom.:

2691

Cov.:

AF XY:

0.181

AC XY:

13473

AN XY:

74286

show subpopulations

African (AFR)

AF:

0.247

AC:

10223

AN:

41416

American (AMR)

AF:

0.121

AC:

1843

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.160

AC:

555

AN:

3468

East Asian (EAS)

AF:

0.238

AC:

1229

AN:

5158

South Asian (SAS)

AF:

0.234

AC:

1125

AN:

4800

European-Finnish (FIN)

AF:

0.144

AC:

1524

AN:

10566

Middle Eastern (MID)

AF:

0.169

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.150

AC:

10208

AN:

67982

Other (OTH)

AF:

0.167

AC:

351

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1119

2238

3358

4477

5596

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

312

624

936

1248

1560

<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:

0.160

Hom.:

4506

Bravo

AF:

0.177

Asia WGS

AF:

0.180

AC:

623

AN:

3478

EpiCase

AF:

0.151

EpiControl

AF:

0.149

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.65

CADD

Benign

0.22

(source)

DANN

Benign

0.75

PhyloP100

-3.3

Mutation Taster

=98/2

polymorphism (auto)

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over