rs554826646

Positions:

• chr2-232524355-G-C
• chr2-232524355-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM2 PM5 BP4_Moderate

The NM_001195129.2(PRSS56):​c.1400G>C​(p.Arg467Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. R467L) has been classified as Likely pathogenic.

• Frequency: Genomes: not found (cov: 34)
• Consequence: PRSS56 NM_001195129.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.312

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM5: Other missense variant is known to change same aminoacid residue: Variant chr2-232524355-G-T is described in Lovd as [Likely_pathogenic].
• BP4: Computational evidence support a benign effect (MetaRNN=0.19742054).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRSS56	NM_001195129.2	c.1400G>C	p.Arg467Pro	missense_variant	11/13	ENST00000617714.2	NP_001182058.1
PRSS56	NM_001369848.1	c.1403G>C	p.Arg468Pro	missense_variant	11/13		NP_001356777.1
PRSS56	XM_047445431.1	c.1496G>C	p.Arg499Pro	missense_variant	10/12		XP_047301387.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRSS56	ENST00000617714.2	c.1400G>C	p.Arg467Pro	missense_variant	11/13	5	NM_001195129.2	ENSP00000479745	P1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Uncertain	0.093	D
BayesDel_noAF	Benign	-0.10
CADD	Benign	19
DANN	Benign	0.90
DEOGEN2	Benign	0.0083	T;T
FATHMM_MKL	Benign	0.040	N
LIST_S2	Benign	0.52	T;T
M_CAP	Pathogenic	0.30	D
MetaRNN	Benign	0.20	T;T
MutationAssessor	Benign	0.90	.;L
PrimateAI	Uncertain	0.55	T
Sift4G	Uncertain	0.0030	D;D
Vest4		0.23
MVP		0.41
GERP RS		2.2
Varity_R		0.38
gMVP		0.41

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: rs554826646; hg19: chr2-233389065;