Variant rs115590586 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001195129.2(PRSS56):c.211G>C(p.Gly71Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000798 in 1,536,000 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. 9/13 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0042 ( 1 hom., cov: 33)

Exomes 𝑓: 0.00042 ( 7 hom. )

Consequence

PRSS56
NM_001195129.2 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.05

Variant links:

Genes affected

PRSS56 (HGNC:39433): (serine protease 56) This gene encodes a protein that contains a peptidase S1 domain and possesses trypsin-like serine protease activity. The encoded protein may play a role in eye development, and mutations in this gene are a cause of autosomal recessive posterior microphthalmos. [provided by RefSeq, Dec 2011]

PRSS56 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0041065216).

BP6

Variant 2-232521821-G-C is Benign according to our data. Variant chr2-232521821-G-C is described in ClinVar as [Benign]. Clinvar id is 538841.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-232521821-G-C is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00425 (647/152320) while in subpopulation AFR AF= 0.0145 (604/41570). AF 95% confidence interval is 0.0136. There are 1 homozygotes in gnomad4. There are 292 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRSS56	NM_001195129.2 linkuse as main transcript	c.211G>C	p.Gly71Arg	missense_variant	3/13	ENST00000617714.2	NP_001182058.1	P0CW18
PRSS56	NM_001369848.1 linkuse as main transcript	c.211G>C	p.Gly71Arg	missense_variant	3/13		NP_001356777.1
PRSS56	XM_047445431.1 linkuse as main transcript	c.211G>C	p.Gly71Arg	missense_variant	3/12		XP_047301387.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRSS56	ENST00000617714.2 linkuse as main transcript	c.211G>C	p.Gly71Arg	missense_variant	3/13	5	NM_001195129.2	ENSP00000479745.1		P0CW18

Frequencies

GnomAD3 genomes

AF:

0.00426

AC:

649

AN:

152202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0146

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00383

GnomAD3 exomes

AF:

0.00102

AC:

137

AN:

134436

Hom.:

AF XY:

0.000820

AC XY:

AN XY:

73212

show subpopulations

Gnomad AFR exome

AF:

0.0174

Gnomad AMR exome

AF:

0.000982

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000242

GnomAD4 exome

AF:

0.000418

AC:

578

AN:

1383680

Hom.:

Cov.:

AF XY:

0.000337

AC XY:

230

AN XY:

682784

show subpopulations

Gnomad4 AFR exome

AF:

0.0148

Gnomad4 AMR exome

AF:

0.00104

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000126

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000102

Gnomad4 OTH exome

AF:

0.00109

GnomAD4 genome

AF:

0.00425

AC:

647

AN:

152320

Hom.:

Cov.:

AF XY:

0.00392

AC XY:

292

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.0145

Gnomad4 AMR

AF:

0.00196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.00379

Alfa

AF:

0.00197

Hom.:

Bravo

AF:

0.00485

ExAC

AF:

0.000943

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Isolated microphthalmia 6

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 15, 2024

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.28

CADD

Benign

DANN

Benign

0.79

DEOGEN2

Benign

0.013

T;T

FATHMM_MKL

Benign

0.29

LIST_S2

Benign

0.60

T;T

MetaRNN

Benign

0.0041

T;T

MutationAssessor

Benign

0.55

.;N

PrimateAI

Uncertain

0.49

Sift4G

Uncertain

0.014

D;D

Vest4

0.13

MVP

0.61

GERP RS

1.4

Varity_R

0.048

gMVP

0.60

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