ENST00000429677.8:c.14G>C

Variant names:

• chr9-33750847-G-C
• rs855551
• ENST00000429677.8:c.14G>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong 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. 13/16 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.00
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -20 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 VariationId is 1259461.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.361 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000429677.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRSS3	NM_001197098.1		c.14G>C	p.Gly5Ala	missense	Exon 1 of 5	NP_001184027.1	P35030
	PRSS3	NM_001197097.3		c.-47+120G>C		intron	N/A	NP_001184026.3	P35030-4
	PRSS3	NM_007343.4		c.-285+120G>C		intron	N/A	NP_031369.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRSS3	ENST00000429677.8	TSL:1	c.14G>C	p.Gly5Ala	missense	Exon 1 of 5	ENSP00000401828.3	P35030-5
	PRSS3	ENST00000342836.9	TSL:1	c.-53+120G>C		intron	N/A	ENSP00000340889.5	A0A7P0MNE9
	PRSS3	ENST00000361005.10	TSL:1	c.-285+120G>C		intron	N/A	ENSP00000354280.6	A0A7P0MP65

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

GnomAD2 exomes AF: 0.110 AC: 1902 AN: 17262 AF XY: 0.115

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 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

African (AFR) AF: 0.377 AC: 8967 AN: 23796

American (AMR) AF: 0.0968 AC: 1309 AN: 13518

Ashkenazi Jewish (ASJ) AF: 0.115 AC: 1976 AN: 17194

East Asian (EAS) AF: 0.0338 AC: 974 AN: 28838

South Asian (SAS) AF: 0.175 AC: 9508 AN: 54470

European-Finnish (FIN) AF: 0.124 AC: 3605 AN: 29076

Middle Eastern (MID) AF: 0.177 AC: 889 AN: 5026

European-Non Finnish (NFE) AF: 0.124 AC: 125176 AN: 1006208

Other (OTH) AF: 0.137 AC: 6991 AN: 50852

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

African (AFR) AF: 0.366 AC: 15147 AN: 41404

American (AMR) AF: 0.116 AC: 1770 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.122 AC: 424 AN: 3472

East Asian (EAS) AF: 0.0361 AC: 185 AN: 5128

South Asian (SAS) AF: 0.179 AC: 861 AN: 4802

European-Finnish (FIN) AF: 0.121 AC: 1280 AN: 10598

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.123 AC: 8363 AN: 67950

Other (OTH) AF: 0.171 AC: 362 AN: 2116

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

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.074
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
PhyloP100		-2.0
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
PromoterAI		-0.019	Neutral
Mutation Taster		=99/1	polymorphism (auto)

Splicing

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

Other links and lift over

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