dbSNP rs6601483: PRSS55:p.Ile270Ile (chr8-10538544-A-C) – ACMG Classification: Benign (-13 pts)

Variant summary

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

The NM_198464.4(PRSS55):c.810A>C(p.Ile270Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.644 in 1,613,812 control chromosomes in the GnomAD database, including 335,908 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 0.64 ( 30939 hom., cov: 32)

Exomes 𝑓: 0.64 ( 304969 hom. )

Consequence

PRSS55
NM_198464.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.551

Publications

19 publications found

Variant links:

Genes affected

PRSS55 (HGNC:30824): (serine protease 55) This gene encodes a member of a group of membrane-anchored chymotrypsin (S1)-like serine proteases. The enocoded protein is primarily expressed in the Leydig and Sertoli cells of the testis and may be involved in male fertility. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Sep 2010]

PRSS55 links:

PRSS51 (HGNC:37321): (serine protease 51) 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]

PRSS51 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=-0.61).

BP7

Synonymous conserved (PhyloP=0.551 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.749 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRSS55	NM_198464.4 link	c.810A>C	p.Ile270Ile	synonymous_variant	Exon 5 of 5	ENST00000328655.8	NP_940866.2	Q6UWB4-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRSS55	ENST00000328655.8 link	c.810A>C	p.Ile270Ile	synonymous_variant	Exon 5 of 5	1	NM_198464.4	ENSP00000333003.3		Q6UWB4-1

Frequencies

GnomAD3 genomes

AF:

0.636

AC:

96621

AN:

151966

Hom.:

30880

Cov.:

show subpopulations

Gnomad AFR

AF:

0.614

Gnomad AMI

AF:

0.355

Gnomad AMR

AF:

0.690

Gnomad ASJ

AF:

0.513

Gnomad EAS

AF:

0.769

Gnomad SAS

AF:

0.692

Gnomad FIN

AF:

0.622

Gnomad MID

AF:

0.532

Gnomad NFE

AF:

0.636

Gnomad OTH

AF:

0.602

GnomAD2 exomes

AF:

0.649

AC:

163036

AN:

251398

AF XY:

0.647

show subpopulations

Gnomad AFR exome

AF:

0.622

Gnomad AMR exome

AF:

0.695

Gnomad ASJ exome

AF:

0.523

Gnomad EAS exome

AF:

0.761

Gnomad FIN exome

AF:

0.613

Gnomad NFE exome

AF:

0.632

Gnomad OTH exome

AF:

0.617

GnomAD4 exome

AF:

0.645

AC:

942144

AN:

1461728

Hom.:

304969

Cov.:

AF XY:

0.644

AC XY:

468282

AN XY:

727176

show subpopulations

African (AFR)

AF:

0.610

AC:

20432

AN:

33480

American (AMR)

AF:

0.693

AC:

30992

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.521

AC:

13628

AN:

26136

East Asian (EAS)

AF:

0.785

AC:

31178

AN:

39700

South Asian (SAS)

AF:

0.679

AC:

58521

AN:

86250

European-Finnish (FIN)

AF:

0.618

AC:

32987

AN:

53418

Middle Eastern (MID)

AF:

0.570

AC:

3279

AN:

5748

European-Non Finnish (NFE)

AF:

0.641

AC:

712524

AN:

1111888

Other (OTH)

AF:

0.639

AC:

38603

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

18534

37069

55603

74138

92672

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

18924

37848

56772

75696

94620

<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:

0.636

AC:

96744

AN:

152084

Hom.:

30939

Cov.:

AF XY:

0.639

AC XY:

47476

AN XY:

74346

show subpopulations

African (AFR)

AF:

0.615

AC:

25489

AN:

41478

American (AMR)

AF:

0.691

AC:

10564

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.513

AC:

1780

AN:

3470

East Asian (EAS)

AF:

0.769

AC:

3967

AN:

5160

South Asian (SAS)

AF:

0.693

AC:

3345

AN:

4824

European-Finnish (FIN)

AF:

0.622

AC:

6574

AN:

10570

Middle Eastern (MID)

AF:

0.541

AC:

159

AN:

294

European-Non Finnish (NFE)

AF:

0.636

AC:

43266

AN:

67978

Other (OTH)

AF:

0.605

AC:

1278

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1853

3706

5558

7411

9264

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

788

1576

2364

3152

3940

<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:

0.650

Hom.:

33729

Bravo

AF:

0.635

Asia WGS

AF:

0.722

AC:

2509

AN:

3478

EpiCase

AF:

0.620

EpiControl

AF:

0.614

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.61

CADD

Benign

8.9

(source)

DANN

Benign

0.81

PhyloP100

0.55

Mutation Taster

=100/0

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