dbSNP rs10485144: PRSS35:c.-20-1237C>T (chr6-83522185-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is . The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_153362.3(PRSS35):c.-20-1237C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0446 in 152,234 control chromosomes in the GnomAD database, including 466 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 0.045 ( 466 hom., cov: 32)

Consequence

PRSS35
NM_153362.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.589

Publications

1 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:

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new If you want to explore the variant's impact on the transcript NM_153362.3, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

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=-0.89).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.151 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153362.3. 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
	PRSS35	NM_153362.3	MANE Select	c.-20-1237C>T		intron	N/A	NP_699193.2	Q8N3Z0
	PRSS35	NM_001170423.2		c.-21+546C>T		intron	N/A	NP_001163894.1	Q8N3Z0

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PRSS35	ENST00000369700.4	TSL:1 MANE Select	c.-20-1237C>T	intron	N/A	ENSP00000358714.3	Q8N3Z0
PRSS35	ENST00000867649.1		c.-21+546C>T	intron	N/A	ENSP00000537708.1
PRSS35	ENST00000867650.1		c.-21+546C>T	intron	N/A	ENSP00000537709.1

Frequencies

GnomAD3 genomes

AF:

0.0446

AC:

6783

AN:

152116

Hom.:

467

Cov.:

show subpopulations

Gnomad AFR

AF:

0.154

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0177

Gnomad ASJ

AF:

0.00231

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000809

Gnomad OTH

AF:

0.0316

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.0446

AC:

6790

AN:

152234

Hom.:

466

Cov.:

AF XY:

0.0429

AC XY:

3193

AN XY:

74428

show subpopulations

African (AFR)

AF:

0.154

AC:

6384

AN:

41522

American (AMR)

AF:

0.0177

AC:

270

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.00231

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.000829

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10606

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000809

AC:

AN:

68014

Other (OTH)

AF:

0.0313

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

300

600

901

1201

1501

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

136

204

272

340

<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:

0.0178

Hom.:

486

Bravo

AF:

0.0520

Asia WGS

AF:

0.0100

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

1.1

(source)

DANN

Benign

0.64

PhyloP100

-0.59

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over