chr2-232522594-C-G

Position:

• chr2-232522594-C-G

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM1 PM2 PP3_Moderate PP5

The NM_001195129.2(PRSS56):​c.526C>G​(p.Arg176Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 33)
• Consequence: PRSS56 NM_001195129.2 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 1.71

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]

ACMG classification

Verdict is Likely_pathogenic. Variant got 7 ACMG points.

• PM1: In a domain Peptidase S1 (size 232) in uniprot entity PRS56_HUMAN there are 6 pathogenic changes around while only 1 benign (86%) in NM_001195129.2
• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.853
• PP5: Variant 2-232522594-C-G is Pathogenic according to our data. Variant chr2-232522594-C-G is described in ClinVar as [Pathogenic]. Clinvar id is 31080.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRSS56	NM_001195129.2	c.526C>G	p.Arg176Gly	missense_variant	5/13	ENST00000617714.2	NP_001182058.1
PRSS56	NM_001369848.1	c.526C>G	p.Arg176Gly	missense_variant	5/13		NP_001356777.1
PRSS56	XM_047445431.1	c.526C>G	p.Arg176Gly	missense_variant	5/12		XP_047301387.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRSS56	ENST00000617714.2	c.526C>G	p.Arg176Gly	missense_variant	5/13	5	NM_001195129.2	ENSP00000479745	P1
PRSS56	ENST00000602410.1	n.94C>G		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Isolated microphthalmia 6 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Mar 11, 2011

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.72
BayesDel_addAF	Pathogenic	0.50	D
BayesDel_noAF	Pathogenic	0.48
CADD	Uncertain	25
DANN	Benign	0.80
DEOGEN2	Uncertain	0.54	D;T
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.87	D;D
M_CAP	Pathogenic	0.97	D
MetaRNN	Pathogenic	0.85	D;D
MutationAssessor	Benign	1.1	.;L
PrimateAI	Uncertain	0.69	T
Sift4G	Uncertain	0.0070	D;D
Vest4		0.60
MVP		0.72
GERP RS		4.7
Varity_R		0.82
gMVP		0.90

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

Other links and lift over

dbSNP: rs387907096; hg19: chr2-233387304;