2-232520492-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BA1

The NM_001195129.2(PRSS56):c.-107C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.252 in 864,374 control chromosomes in the GnomAD database, including 29,660 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.28 (6463 hom., cov: 32)
  • Exomes 𝑓: 0.25 (23197 hom.)
• Consequence: PRSS56 NM_001195129.2 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.175

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BP6: Variant 2-232520492-C-T is Benign according to our data. Variant chr2-232520492-C-T is described in ClinVar as [Benign]. Clinvar id is 1287863.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.456 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRSS56	NM_001195129.2	c.-107C>T		5_prime_UTR_variant	1/13	ENST00000617714.2
PRSS56	NM_001369848.1	c.-107C>T		5_prime_UTR_variant	1/13
PRSS56	XM_047445431.1	c.-107C>T		5_prime_UTR_variant	1/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRSS56	ENST00000617714.2	c.-107C>T		5_prime_UTR_variant	1/13	5	NM_001195129.2	P1

Frequencies

GnomAD3 genomes AF: 0.283 AC: 43023 AN: 151926 Hom.: 6458 Cov.: 32

Gnomad AFR AF: 0.371

Gnomad AMI AF: 0.132

Gnomad AMR AF: 0.218

Gnomad ASJ AF: 0.246

Gnomad EAS AF: 0.471

Gnomad SAS AF: 0.220

Gnomad FIN AF: 0.339

Gnomad MID AF: 0.220

Gnomad NFE AF: 0.231

Gnomad OTH AF: 0.251

GnomAD4 exome AF: 0.246 AC: 175032 AN: 712328 Hom.: 23197 Cov.: 9 AF XY: 0.244 AC XY: 90939 AN XY: 373264

Gnomad4 AFR exome AF: 0.375

Gnomad4 AMR exome AF: 0.211

Gnomad4 ASJ exome AF: 0.242

Gnomad4 EAS exome AF: 0.459

Gnomad4 SAS exome AF: 0.219

Gnomad4 FIN exome AF: 0.320

Gnomad4 NFE exome AF: 0.227

Gnomad4 OTH exome AF: 0.252

GnomAD4 genome AF: 0.283 AC: 43052 AN: 152046 Hom.: 6463 Cov.: 32 AF XY: 0.286 AC XY: 21242 AN XY: 74306

Gnomad4 AFR AF: 0.371

Gnomad4 AMR AF: 0.217

Gnomad4 ASJ AF: 0.246

Gnomad4 EAS AF: 0.471

Gnomad4 SAS AF: 0.221

Gnomad4 FIN AF: 0.339

Gnomad4 NFE AF: 0.231

Gnomad4 OTH AF: 0.248

Alfa AF: 0.277 Hom.: 856

Bravo AF: 0.279

Asia WGS AF: 0.277 AC: 962 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 26, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
Cadd	Benign	15
Dann	Benign	0.83

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: rs2741294; hg19: chr2-233385202; COSMIC: COSV71930120; COSMIC: COSV71930120;