ENST00000429677.8:c.14G>A

Variant names:

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

Variant summary

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

The ENST00000429677.8(PRSS3):​c.14G>A​(p.Gly5Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000114 in 1,229,134 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/14 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. G5A) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.000011 (0 hom.)
• Consequence: PRSS3 ENST00000429677.8 missense
• Clinical Significance: Not reported in ClinVar
• 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 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=0.07593265).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRSS3	NM_001197098.1	c.14G>A	p.Gly5Glu	missense_variant	Exon 1 of 5		NP_001184027.1
PRSS3	NM_001197097.3	c.-47+120G>A		intron_variant	Intron 1 of 5		NP_001184026.3
PRSS3	NM_007343.4	c.-285+120G>A		intron_variant	Intron 1 of 4		NP_031369.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRSS3	ENST00000429677.8	c.14G>A	p.Gly5Glu	missense_variant	Exon 1 of 5	1		ENSP00000401828.3
PRSS3	ENST00000342836.9	c.-53+120G>A		intron_variant	Intron 1 of 5	1		ENSP00000340889.5
PRSS3	ENST00000361005.10	c.-285+120G>A		intron_variant	Intron 1 of 4	1		ENSP00000354280.6

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.0000114 AC: 14 AN: 1229134 Hom.: 0 Cov.: 34 AF XY: 0.00000843 AC XY: 5 AN XY: 593062

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: 0.0000139

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	0.58
DANN	Benign	0.83
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.0043	N
LIST_S2	Benign	0.25	T
M_CAP	Benign	0.0047	T
MetaRNN	Benign	0.076	T
MetaSVM	Benign	-0.57	T
PROVEAN	Benign	-0.26	N
REVEL	Benign	0.11
Sift	Benign	0.092	T
Sift4G	Benign	0.62	T
Vest4		0.14
MutPred		0.35		Loss of catalytic residue at A4 (P = 0.0582);
MVP		0.10
ClinPred		0.046	T
GERP RS		-3.9

Splicing

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: chr9-33750845;