rs1550094

Variant names:

• chr2-232520686-G-A
• rs1550094
• NM_001195129.2:c.88G>A

Your query was ambiguous. Multiple possible variants found:

• chr2-232520686-G-A
• chr2-232520686-G-C
• chr2-232520686-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001195129.2(PRSS56):​c.88G>A​(p.Ala30Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.694 in 1,530,984 control chromosomes in the GnomAD database, including 371,791 homozygotes. In-silico tool predicts a benign outcome for this variant. 9/13 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.65 (32965 hom., cov: 32)
  • Exomes 𝑓: 0.70 (338826 hom.)
• Consequence: PRSS56 NM_001195129.2 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.922
• Publications: 38 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=5.478455E-7).
• BP6: Variant 2-232520686-G-A is Benign according to our data. Variant chr2-232520686-G-A is described in ClinVar as Benign. ClinVar VariationId is 677180.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.879 is higher than 0.05.

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.88G>A	p.Ala30Thr	missense	Exon 1 of 13	NP_001182058.1	P0CW18
	PRSS56	NM_001369848.1		c.88G>A	p.Ala30Thr	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.88G>A	p.Ala30Thr	missense	Exon 1 of 13	ENSP00000479745.1	P0CW18

Frequencies

GnomAD3 genomes AF: 0.648 AC: 98494 AN: 151898 Hom.: 32938 Cov.: 32

Gnomad AFR AF: 0.484

Gnomad AMI AF: 0.586

Gnomad AMR AF: 0.707

Gnomad ASJ AF: 0.687

Gnomad EAS AF: 0.901

Gnomad SAS AF: 0.698

Gnomad FIN AF: 0.763

Gnomad MID AF: 0.636

Gnomad NFE AF: 0.694

Gnomad OTH AF: 0.622

GnomAD2 exomes AF: 0.717 AC: 95950 AN: 133744 AF XY: 0.714

Gnomad AFR exome AF: 0.470

Gnomad AMR exome AF: 0.785

Gnomad ASJ exome AF: 0.699

Gnomad EAS exome AF: 0.899

Gnomad FIN exome AF: 0.752

Gnomad NFE exome AF: 0.695

Gnomad OTH exome AF: 0.693

GnomAD4 exome AF: 0.699 AC: 963286 AN: 1378968 Hom.: 338826 Cov.: 33 AF XY: 0.699 AC XY: 475195 AN XY: 680082

African (AFR) AF: 0.472 AC: 14872 AN: 31490

American (AMR) AF: 0.775 AC: 27623 AN: 35630

Ashkenazi Jewish (ASJ) AF: 0.696 AC: 17463 AN: 25096

East Asian (EAS) AF: 0.875 AC: 31187 AN: 35654

South Asian (SAS) AF: 0.688 AC: 54461 AN: 79102

European-Finnish (FIN) AF: 0.757 AC: 25631 AN: 33868

Middle Eastern (MID) AF: 0.620 AC: 3513 AN: 5668

European-Non Finnish (NFE) AF: 0.697 AC: 748627 AN: 1074770

Other (OTH) AF: 0.692 AC: 39909 AN: 57690

GnomAD4 genome AF: 0.648 AC: 98559 AN: 152016 Hom.: 32965 Cov.: 32 AF XY: 0.655 AC XY: 48679 AN XY: 74314

African (AFR) AF: 0.484 AC: 20065 AN: 41440

American (AMR) AF: 0.707 AC: 10814 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.687 AC: 2386 AN: 3472

East Asian (EAS) AF: 0.901 AC: 4645 AN: 5158

South Asian (SAS) AF: 0.698 AC: 3364 AN: 4818

European-Finnish (FIN) AF: 0.763 AC: 8075 AN: 10582

Middle Eastern (MID) AF: 0.636 AC: 187 AN: 294

European-Non Finnish (NFE) AF: 0.694 AC: 47169 AN: 67942

Other (OTH) AF: 0.626 AC: 1322 AN: 2112

Alfa AF: 0.689 Hom.: 75029

Bravo AF: 0.640

TwinsUK AF: 0.706 AC: 2616

ALSPAC AF: 0.708 AC: 2729

ExAC AF: 0.609 AC: 10624

Asia WGS AF: 0.754 AC: 2621 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Isolated microphthalmia 6 (2)
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.057
BayesDel_addAF	Benign	-0.58	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	16
DANN	Benign	0.88
DEOGEN2	Benign	0.0041	T
FATHMM_MKL	Benign	0.049	N
LIST_S2	Benign	0.18	T
MetaRNN	Benign	5.5e-7	T
MutationAssessor	Benign	-0.34	N
PhyloP100		0.92
PrimateAI	Uncertain	0.51	T
Sift4G	Benign	1.0	T
Vest4		0.029
GERP RS		2.3
PromoterAI		-0.020	Neutral
Varity_R		0.039
gMVP		0.28
Mutation Taster		=99/1	polymorphism (auto)

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: rs1550094; hg19: chr2-233385396; COSMIC: COSV71930103; COSMIC: COSV71930103;