Genetic Variant ENSG00000255439:c.284-1175C>T (chr16-31089001-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The ENST00000529564.1(ENSG00000255439):c.284-1175C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00214 in 1,387,514 control chromosomes in the GnomAD database, including 28 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 0.0076 ( 16 hom., cov: 32)

Exomes 𝑓: 0.0015 ( 12 hom. )

Consequence

ENSG00000255439
ENST00000529564.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -4.14

Publications

1 publications found

Variant links:

Genes affected

ENSG00000255439 (HGNC:):

ENSG00000255439 links:

PRSS53 (HGNC:34407): (serine protease 53) 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]

PRSS53 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00764 (1164/152376) while in subpopulation AFR AF = 0.0242 (1005/41584). AF 95% confidence interval is 0.0229. There are 16 homozygotes in GnomAd4. There are 552 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 16 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000529564.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRSS53	NM_001039503.3	MANE Select	c.-192C>T		upstream_gene	N/A	NP_001034592.1	Q2L4Q9

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ENSG00000255439	ENST00000529564.1	TSL:4	c.284-1175C>T	intron	N/A	ENSP00000431371.1	E9PLN8
ENSG00000255439	ENST00000533518.5	TSL:1	n.*43-1175C>T	intron	N/A	ENSP00000433035.1	H0YD56
ENSG00000255439	ENST00000532364.1	TSL:4	c.174-2103C>T	intron	N/A	ENSP00000460316.1	I3L3B4

Frequencies

GnomAD3 genomes

AF:

0.00764

AC:

1164

AN:

152258

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0243

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00314

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00115

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00122

Gnomad OTH

AF:

0.00669

GnomAD4 exome

AF:

0.00146

AC:

1807

AN:

1235138

Hom.:

Cov.:

AF XY:

0.00140

AC XY:

841

AN XY:

599814

show subpopulations

African (AFR)

AF:

0.0274

AC:

755

AN:

27554

American (AMR)

AF:

0.00200

AC:

AN:

21470

Ashkenazi Jewish (ASJ)

AF:

0.000107

AC:

AN:

18702

East Asian (EAS)

AF:

0.000409

AC:

AN:

34236

South Asian (SAS)

AF:

0.000127

AC:

AN:

62792

European-Finnish (FIN)

AF:

0.000641

AC:

AN:

29644

Middle Eastern (MID)

AF:

0.00245

AC:

AN:

4078

European-Non Finnish (NFE)

AF:

0.000840

AC:

827

AN:

984926

Other (OTH)

AF:

0.00249

AC:

129

AN:

51736

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

168

253

337

421

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

144

192

240

<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:

0.00764

AC:

1164

AN:

152376

Hom.:

Cov.:

AF XY:

0.00741

AC XY:

552

AN XY:

74518

show subpopulations

African (AFR)

AF:

0.0242

AC:

1005

AN:

41584

American (AMR)

AF:

0.00314

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.000576

AC:

AN:

3472

East Asian (EAS)

AF:

0.00115

AC:

AN:

5196

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.000188

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00122

AC:

AN:

68036

Other (OTH)

AF:

0.00756

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

124

186

248

310

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00363

Hom.:

Bravo

AF:

0.00868

Asia WGS

AF:

0.00346

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.010

(source)

DANN

Benign

0.29

PhyloP100

-4.1

PromoterAI

0.019

Neutral

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over