rs730882161

Positions:

• chr2-232523942-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2 PP3_Moderate PP5

The NM_001195129.2(PRSS56):​c.1183T>C​(p.Cys395Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000000738 in 1,355,256 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 34)
  • Exomes 𝑓: 7.4e-7 (0 hom.)
• Consequence: PRSS56 NM_001195129.2 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 4.98

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 Uncertain_significance. Variant got 5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.923
• PP5: Variant 2-232523942-T-C is Pathogenic according to our data. Variant chr2-232523942-T-C is described in ClinVar as [Pathogenic]. Clinvar id is 183174.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.1183T>C	p.Cys395Arg	missense_variant	9/13	ENST00000617714.2	NP_001182058.1
PRSS56	NM_001369848.1	c.1186T>C	p.Cys396Arg	missense_variant	9/13		NP_001356777.1
PRSS56	XM_047445431.1	c.1186T>C	p.Cys396Arg	missense_variant	9/12		XP_047301387.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRSS56	ENST00000617714.2	c.1183T>C	p.Cys395Arg	missense_variant	9/13	5	NM_001195129.2	ENSP00000479745	P1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD3 exomes AF: 0.00000948 AC: 1 AN: 105456 Hom.: 0 AF XY: 0.0000173 AC XY: 1 AN XY: 57956

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000487

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: 0.00

GnomAD4 exome AF: 7.38e-7 AC: 1 AN: 1355256 Hom.: 0 Cov.: 35 AF XY: 0.00000150 AC XY: 1 AN XY: 666296

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000314

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

Bravo AF: 0.00000756

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

Jan 01, 2011

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.97
BayesDel_addAF	Pathogenic	0.39	D
BayesDel_noAF	Pathogenic	0.47
CADD	Pathogenic	26
DANN	Benign	0.92
DEOGEN2	Benign	0.21	T;T
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.63	T;T
M_CAP	Pathogenic	0.99	D
MetaRNN	Pathogenic	0.92	D;D
MutationAssessor	Benign	0.97	.;L
PrimateAI	Pathogenic	0.95	D
Sift4G	Pathogenic	0.0	D;D
Vest4		0.93
MVP		0.70
GERP RS		3.9
Varity_R		0.84
gMVP		0.91

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: rs730882161; hg19: chr2-233388652;