chr2-232521821-G-A

Variant names:

• chr2-232521821-G-A
• NM_001195129.2:c.211G>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.211G>A​(p.Gly71Arg) 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 1,383,682 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 9/14 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Benign in Lovd.

• 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: 1.05

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=0.15383592).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRSS56	NM_001195129.2	c.211G>A	p.Gly71Arg	missense_variant	Exon 3 of 13	ENST00000617714.2	NP_001182058.1
PRSS56	NM_001369848.1	c.211G>A	p.Gly71Arg	missense_variant	Exon 3 of 13		NP_001356777.1
PRSS56	XM_047445431.1	c.211G>A	p.Gly71Arg	missense_variant	Exon 3 of 12		XP_047301387.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRSS56	ENST00000617714.2	c.211G>A	p.Gly71Arg	missense_variant	Exon 3 of 13	5	NM_001195129.2	ENSP00000479745.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.23e-7 AC: 1 AN: 1383682 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 682786

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.27e-7

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	Benign	0.12
BayesDel_addAF	Benign	-0.028	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	18
DANN	Benign	0.83
DEOGEN2	Benign	0.013	T;T
FATHMM_MKL	Benign	0.27	N
LIST_S2	Benign	0.60	T;T
M_CAP	Uncertain	0.27	D
MetaRNN	Benign	0.15	T;T
MutationAssessor	Benign	0.55	.;N
PrimateAI	Uncertain	0.49	T
Sift4G	Uncertain	0.014	D;D
Vest4		0.13
MVP		0.61
GERP RS		1.4
Varity_R		0.048
gMVP		0.60

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		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: chr2-233386531;