chr2-232521367-C-A

Variant names:

• chr2-232521367-C-A
• rs751017393
• NM_001195129.2:c.144C>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001195129.2(PRSS56):​c.144C>A​(p.Ser48Arg) 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. 10/14 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: PRSS56 NM_001195129.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.55

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.084563255).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRSS56	NM_001195129.2	c.144C>A	p.Ser48Arg	missense_variant	Exon 2 of 13	ENST00000617714.2	NP_001182058.1
PRSS56	NM_001369848.1	c.144C>A	p.Ser48Arg	missense_variant	Exon 2 of 13		NP_001356777.1
PRSS56	XM_047445431.1	c.144C>A	p.Ser48Arg	missense_variant	Exon 2 of 12		XP_047301387.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRSS56	ENST00000617714.2	c.144C>A	p.Ser48Arg	missense_variant	Exon 2 of 13	5	NM_001195129.2	ENSP00000479745.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.30
BayesDel_addAF	Benign	-0.027	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	7.0
DANN	Benign	0.88
DEOGEN2	Benign	0.023	T;T
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.51	T;T
M_CAP	Pathogenic	0.45	D
MetaRNN	Benign	0.085	T;T
MutationAssessor	Benign	0.69	.;N
PrimateAI	Benign	0.47	T
Sift4G	Benign	0.071	T;T
Vest4		0.14
MVP		0.37
GERP RS		-1.9
Varity_R		0.094
gMVP		0.75

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: rs751017393; hg19: chr2-233386077; COSMIC: COSV51323614; COSMIC: COSV51323614;