Variant 1-227816139-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_183062.3(PRSS38):c.198G>A(p.Ala66Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00214 in 1,613,748 control chromosomes in the GnomAD database, including 63 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0041 ( 11 hom., cov: 32)

Exomes 𝑓: 0.0019 ( 52 hom. )

Consequence

PRSS38
NM_183062.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.67

Variant links:

Genes affected

PRSS38 (HGNC:29625): (serine protease 38) 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]

PRSS38 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP6

Variant 1-227816139-G-A is Benign according to our data. Variant chr1-227816139-G-A is described in ClinVar as [Benign]. Clinvar id is 771320.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.67 with no splicing effect.

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00407 (620/152284) while in subpopulation AMR AF= 0.0308 (472/15300). AF 95% confidence interval is 0.0286. There are 11 homozygotes in gnomad4. There are 318 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 11 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRSS38	NM_183062.3 linkuse as main transcript	c.198G>A	p.Ala66Ala	synonymous_variant	2/5	ENST00000366757.4	NP_898885.1	A1L453
PRSS38	NM_001374657.2 linkuse as main transcript	c.198G>A	p.Ala66Ala	synonymous_variant	2/4		NP_001361586.1
PRSS38	XM_011544175.3 linkuse as main transcript	c.198G>A	p.Ala66Ala	synonymous_variant	2/5		XP_011542477.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRSS38	ENST00000366757.4 linkuse as main transcript	c.198G>A	p.Ala66Ala	synonymous_variant	2/5	1	NM_183062.3	ENSP00000355719.3		A1L453

Frequencies

GnomAD3 genomes

AF:

0.00407

AC:

620

AN:

152166

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000579

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0310

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0155

Gnomad SAS

AF:

0.00207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000162

Gnomad OTH

AF:

0.0105

GnomAD3 exomes

AF:

0.00794

AC:

1987

AN:

250338

Hom.:

AF XY:

0.00624

AC XY:

845

AN XY:

135446

show subpopulations

Gnomad AFR exome

AF:

0.000556

Gnomad AMR exome

AF:

0.0457

Gnomad ASJ exome

AF:

0.0000996

Gnomad EAS exome

AF:

0.0180

Gnomad SAS exome

AF:

0.00105

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.0000798

Gnomad OTH exome

AF:

0.00376

GnomAD4 exome

AF:

0.00193

AC:

2827

AN:

1461464

Hom.:

Cov.:

AF XY:

0.00173

AC XY:

1259

AN XY:

727072

show subpopulations

Gnomad4 AFR exome

AF:

0.000448

Gnomad4 AMR exome

AF:

0.0443

Gnomad4 ASJ exome

AF:

0.000115

Gnomad4 EAS exome

AF:

0.0137

Gnomad4 SAS exome

AF:

0.00112

Gnomad4 FIN exome

AF:

0.0000188

Gnomad4 NFE exome

AF:

0.0000360

Gnomad4 OTH exome

AF:

0.00238

GnomAD4 genome

AF:

0.00407

AC:

620

AN:

152284

Hom.:

Cov.:

AF XY:

0.00427

AC XY:

318

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.000577

Gnomad4 AMR

AF:

0.0308

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0155

Gnomad4 SAS

AF:

0.00228

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000162

Gnomad4 OTH

AF:

0.0104

Alfa

AF:

0.000410

Hom.:

Bravo

AF:

0.00779

Asia WGS

AF:

0.00318

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 25, 2017	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

4.9

DANN

Benign

0.72

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