Genetic Variant NM_001195129.2:c.1555G>C (chr2-232525249-G-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 4P and 4B. PS1BP4_Strong

The NM_001195129.2(PRSS56):c.1555G>C(p.Gly519Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000125 in 1,361,458 control chromosomes in the GnomAD database, including 1 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. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely pathogenic in ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000012 ( 1 hom. )

Consequence

PRSS56
NM_001195129.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.19

Publications

1 publications found

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 Gene-Disease associations (from GenCC):

isolated microphthalmia 6
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: PanelApp Australia, G2P, Labcorp Genetics (formerly Invitae)
nanophthalmia
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

PRSS56 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PS1

Transcript NM_001195129.2 (PRSS56) is affected with MISSENSE_VARIANT having same AA change as one Pathogenic present in ClinVar.

BP4

Computational evidence support a benign effect (MetaRNN=0.013643622).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRSS56	NM_001195129.2 link	c.1555G>C	p.Gly519Arg	missense_variant	Exon 13 of 13	ENST00000617714.2	NP_001182058.1	P0CW18
PRSS56	NM_001369848.1 link	c.1558G>C	p.Gly520Arg	missense_variant	Exon 13 of 13		NP_001356777.1
PRSS56	XM_047445431.1 link	c.1651G>C	p.Gly551Arg	missense_variant	Exon 12 of 12		XP_047301387.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRSS56	ENST00000617714.2 link	c.1555G>C	p.Gly519Arg	missense_variant	Exon 13 of 13	5	NM_001195129.2	ENSP00000479745.1		P0CW18

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000262

AC:

AN:

114572

AF XY:

0.0000480

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000125

AC:

AN:

1361458

Hom.:

Cov.:

AF XY:

0.0000149

AC XY:

AN XY:

669058

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30918

American (AMR)

AF:

0.00

AC:

AN:

33124

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23928

East Asian (EAS)

AF:

0.00

AC:

AN:

35304

South Asian (SAS)

AF:

0.000196

AC:

AN:

76570

European-Finnish (FIN)

AF:

0.00

AC:

AN:

32788

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5588

European-Non Finnish (NFE)

AF:

0.00000188

AC:

AN:

1066502

Other (OTH)

AF:

0.00

AC:

AN:

56736

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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

Cov.:

ExAC

AF:

0.0000518

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.75

BayesDel_addAF

Pathogenic

0.34

BayesDel_noAF

Pathogenic

0.51

CADD

Pathogenic

(source)

DANN

Benign

0.90

DEOGEN2

Benign

0.068

T;T

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.79

T;T

MetaRNN

Benign

0.014

T;T

MutationAssessor

Benign

0.97

.;L

PhyloP100

4.2

PrimateAI

Uncertain

0.76

Sift4G

Pathogenic

0.0

D;D

Vest4

0.84

MVP

0.70

GERP RS

3.2

Varity_R

0.088

gMVP

0.85

Mutation Taster

=83/17

polymorphism

(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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over