9-33750847-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000429677.8(PRSS3):c.14G>C(p.Gly5Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.136 in 1,380,954 control chromosomes in the GnomAD database, including 15,434 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/13 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.19 (3715 hom., cov: 31)
  • Exomes 𝑓: 0.13 (11719 hom.)
• Consequence: PRSS3 ENST00000429677.8 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.00

Genes affected

PRSS3 (HGNC:9486): (serine protease 3) This gene encodes a trypsinogen, which is a member of the trypsin family of serine proteases. This enzyme is expressed in the brain and pancreas and is resistant to common trypsin inhibitors. It is active on peptide linkages involving the carboxyl group of lysine or arginine. This gene is localized to the locus of T cell receptor beta variable orphans on chromosome 9. Four transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Oct 2010]

UBE2R2-AS1 (HGNC:49911): (UBE2R2 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.6629696E-4).
• BP6: Variant 9-33750847-G-C is Benign according to our data. Variant chr9-33750847-G-C is described in ClinVar as [Benign]. Clinvar id is 1259461.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.361 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UBE2R2-AS1	NR_170204.1	n.559-12431C>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UBE2R2-AS1	ENST00000705030.1	n.644-12431C>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.188 AC: 28474 AN: 151856 Hom.: 3699 Cov.: 31

Gnomad AFR AF: 0.365

Gnomad AMI AF: 0.107

Gnomad AMR AF: 0.116

Gnomad ASJ AF: 0.122

Gnomad EAS AF: 0.0360

Gnomad SAS AF: 0.178

Gnomad FIN AF: 0.121

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.123

Gnomad OTH AF: 0.173

GnomAD3 exomes AF: 0.110 AC: 1902 AN: 17262 Hom.: 169 AF XY: 0.115 AC XY: 1095 AN XY: 9542

Gnomad AFR exome AF: 0.359

Gnomad AMR exome AF: 0.0812

Gnomad ASJ exome AF: 0.147

Gnomad EAS exome AF: 0.0285

Gnomad SAS exome AF: 0.171

Gnomad FIN exome AF: 0.0848

Gnomad NFE exome AF: 0.111

Gnomad OTH exome AF: 0.110

GnomAD4 exome AF: 0.130 AC: 159395 AN: 1228978 Hom.: 11719 Cov.: 34 AF XY: 0.130 AC XY: 76996 AN XY: 592968

Gnomad4 AFR exome AF: 0.377

Gnomad4 AMR exome AF: 0.0968

Gnomad4 ASJ exome AF: 0.115

Gnomad4 EAS exome AF: 0.0338

Gnomad4 SAS exome AF: 0.175

Gnomad4 FIN exome AF: 0.124

Gnomad4 NFE exome AF: 0.124

Gnomad4 OTH exome AF: 0.137

GnomAD4 genome AF: 0.188 AC: 28537 AN: 151976 Hom.: 3715 Cov.: 31 AF XY: 0.187 AC XY: 13887 AN XY: 74296

Gnomad4 AFR AF: 0.366

Gnomad4 AMR AF: 0.116

Gnomad4 ASJ AF: 0.122

Gnomad4 EAS AF: 0.0361

Gnomad4 SAS AF: 0.179

Gnomad4 FIN AF: 0.121

Gnomad4 NFE AF: 0.123

Gnomad4 OTH AF: 0.171

Alfa AF: 0.161 Hom.: 318

Bravo AF: 0.193

TwinsUK AF: 0.133 AC: 495

ALSPAC AF: 0.130 AC: 502

ExAC AF: 0.0405 AC: 1141

Asia WGS AF: 0.109 AC: 377 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 15, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.61	T
BayesDel_noAF	Benign	-0.50
Cadd	Benign	0.013
Dann	Benign	0.41
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.0090	N
LIST_S2	Benign	0.27	T
MetaRNN	Benign	0.00017	T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	P;P;P
PROVEAN	Benign	1.1	N
REVEL	Benign	0.090
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Vest4		0.036
ClinPred		0.0055	T
GERP RS		-3.9

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs855551; hg19: chr9-33750845; COSMIC: COSV61554483;