chr2-232525249-G-C

Variant names:

• chr2-232525249-G-C
• rs730882162
• NM_001195129.2:c.1555G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 4P and 4B. PS1 BP4_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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.19
• Publications: 1 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: 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).

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.1555G>C	p.Gly519Arg	missense	Exon 13 of 13	NP_001182058.1	P0CW18
	PRSS56	NM_001369848.1		c.1558G>C	p.Gly520Arg	missense	Exon 13 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.1555G>C	p.Gly519Arg	missense	Exon 13 of 13	ENSP00000479745.1	P0CW18

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000262 AC: 3 AN: 114572 AF XY: 0.0000480

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: 17 AN: 1361458 Hom.: 1 Cov.: 36 AF XY: 0.0000149 AC XY: 10 AN XY: 669058

African (AFR) AF: 0.00 AC: 0 AN: 30918

American (AMR) AF: 0.00 AC: 0 AN: 33124

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23928

East Asian (EAS) AF: 0.00 AC: 0 AN: 35304

South Asian (SAS) AF: 0.000196 AC: 15 AN: 76570

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32788

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5588

European-Non Finnish (NFE) AF: 0.00000188 AC: 2 AN: 1066502

Other (OTH) AF: 0.00 AC: 0 AN: 56736

GnomAD4 genome Cov.: 33

ExAC AF: 0.0000518 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.75
BayesDel_addAF	Pathogenic	0.34	D
BayesDel_noAF	Pathogenic	0.51
CADD	Pathogenic	26
DANN	Benign	0.90
DEOGEN2	Benign	0.068	T
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.79	T
MetaRNN	Benign	0.014	T
MutationAssessor	Benign	0.97	L
PhyloP100		4.2
PrimateAI	Uncertain	0.76	T
Sift4G	Pathogenic	0.0	D
Vest4		0.84
MVP		0.70
GERP RS		3.2
Varity_R		0.088
gMVP		0.85
Mutation Taster		=83/17	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: rs730882162; hg19: chr2-233389959;