rs387907096

Variant names:

• chr2-232522594-C-A
• NM_001195129.2:c.526C>A

Your query was ambiguous. Multiple possible variants found:

• chr2-232522594-C-A
• chr2-232522594-C-G
• chr2-232522594-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM1 PM2 PP3

The NM_001195129.2(PRSS56):​c.526C>A​(p.Arg176Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000723 in 1,383,018 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: PRSS56 NM_001195129.2 missense
• Clinical Significance: Not reported in ClinVar
• 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 Uncertain_significance. Variant got 5 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, 0.761

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRSS56	NM_001195129.2	c.526C>A	p.Arg176Ser	missense_variant	Exon 5 of 13	ENST00000617714.2	NP_001182058.1
PRSS56	NM_001369848.1	c.526C>A	p.Arg176Ser	missense_variant	Exon 5 of 13		NP_001356777.1
PRSS56	XM_047445431.1	c.526C>A	p.Arg176Ser	missense_variant	Exon 5 of 12		XP_047301387.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRSS56	ENST00000617714.2	c.526C>A	p.Arg176Ser	missense_variant	Exon 5 of 13	5	NM_001195129.2	ENSP00000479745.1
PRSS56	ENST00000602410.1	n.94C>A		non_coding_transcript_exon_variant	Exon 1 of 2	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.23e-7 AC: 1 AN: 1383018 Hom.: 0 Cov.: 33 AF XY: 0.00000147 AC XY: 1 AN XY: 682482

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000280

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.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.83
BayesDel_addAF	Pathogenic	0.31	D
BayesDel_noAF	Pathogenic	0.21
CADD	Uncertain	25
DANN	Benign	0.89
DEOGEN2	Uncertain	0.49	T;T
FATHMM_MKL	Benign	0.75	D
LIST_S2	Uncertain	0.86	D;D
M_CAP	Pathogenic	0.96	D
MetaRNN	Pathogenic	0.76	D;D
MutationAssessor	Benign	-0.13	.;N
PrimateAI	Uncertain	0.70	T
Sift4G	Uncertain	0.035	D;D
Vest4		0.64
MVP		0.47
GERP RS		4.7
Varity_R		0.64
gMVP		0.84

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-233387304;