rs1199486833

Variant names:

• chr2-232520652-C-A
• rs1199486833
• NM_001195129.2:c.54C>A

Your query was ambiguous. Multiple possible variants found:

• chr2-232520652-C-A
• chr2-232520652-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001195129.2(PRSS56):​c.54C>A​(p.His18Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000217 in 1,383,730 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/14 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H18R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000022 (0 hom.)
• Consequence: PRSS56 NM_001195129.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.60
• Publications: 0 publications found

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: G2P, Labcorp Genetics (formerly Invitae)
• nanophthalmia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.03678742).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001195129.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRSS56	NM_001195129.2	MANE Select	c.54C>A	p.His18Gln	missense	Exon 1 of 13	NP_001182058.1	P0CW18
	PRSS56	NM_001369848.1		c.54C>A	p.His18Gln	missense	Exon 1 of 13	NP_001356777.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRSS56	ENST00000617714.2	TSL:5 MANE Select	c.54C>A	p.His18Gln	missense	Exon 1 of 13	ENSP00000479745.1	P0CW18

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000217 AC: 3 AN: 1383730 Hom.: 0 Cov.: 31 AF XY: 0.00000293 AC XY: 2 AN XY: 682822

African (AFR) AF: 0.00 AC: 0 AN: 31592

American (AMR) AF: 0.00 AC: 0 AN: 35696

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25180

East Asian (EAS) AF: 0.00 AC: 0 AN: 35732

South Asian (SAS) AF: 0.0000252 AC: 2 AN: 79232

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33898

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5692

European-Non Finnish (NFE) AF: 9.27e-7 AC: 1 AN: 1078804

Other (OTH) AF: 0.00 AC: 0 AN: 57904

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	0.0010
DANN	Benign	0.69
DEOGEN2	Benign	0.013	T
FATHMM_MKL	Benign	0.033	N
LIST_S2	Benign	0.36	T
M_CAP	Benign	0.045	D
MetaRNN	Benign	0.037	T
MutationAssessor	Benign	0.55	N
PhyloP100		-3.6
PrimateAI	Benign	0.46	T
Sift4G	Benign	0.20	T
Vest4		0.052
MVP		0.14
GERP RS		-8.1
PromoterAI		0.0031	Neutral
Varity_R		0.060
gMVP		0.16
Mutation Taster		=90/10	polymorphism

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

Other links and lift over

dbSNP: rs1199486833; hg19: chr2-233385362;