NM_002771.4:c.200+256A>T

Variant names:

• chr9-33797058-A-T
• rs83921
• NM_002771.4:c.200+256A>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002771.4(PRSS3):​c.200+256A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.593 in 151,994 control chromosomes in the GnomAD database, including 27,079 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.59 (27079 hom., cov: 32)
• Consequence: PRSS3 NM_002771.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0850
• Publications: 6 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 9-33797058-A-T is Benign according to our data. Variant chr9-33797058-A-T is described in ClinVar as Benign. ClinVar VariationId is 1263618.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.793 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002771.4. 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_002771.4	MANE Select	c.200+256A>T		intron	N/A	NP_002762.3
	PRSS3	NM_001197097.3		c.242+256A>T		intron	N/A	NP_001184026.3	P35030-4
	PRSS3	NM_001197098.1		c.179+256A>T		intron	N/A	NP_001184027.1	P35030

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRSS3	ENST00000379405.4	TSL:1 MANE Select	c.200+256A>T		intron	N/A	ENSP00000368715.3	P35030-3
	PRSS3	ENST00000342836.9	TSL:1	c.236+256A>T		intron	N/A	ENSP00000340889.5	A0A7P0MNE9
	PRSS3	ENST00000429677.8	TSL:1	c.179+256A>T		intron	N/A	ENSP00000401828.3	P35030-5

Frequencies

GnomAD3 genomes AF: 0.593 AC: 90095 AN: 151876 Hom.: 27076 Cov.: 32

Gnomad AFR AF: 0.509

Gnomad AMI AF: 0.493

Gnomad AMR AF: 0.653

Gnomad ASJ AF: 0.715

Gnomad EAS AF: 0.813

Gnomad SAS AF: 0.528

Gnomad FIN AF: 0.567

Gnomad MID AF: 0.718

Gnomad NFE AF: 0.616

Gnomad OTH AF: 0.631

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.593 AC: 90123 AN: 151994 Hom.: 27079 Cov.: 32 AF XY: 0.592 AC XY: 43988 AN XY: 74298

African (AFR) AF: 0.509 AC: 21076 AN: 41432

American (AMR) AF: 0.652 AC: 9959 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.715 AC: 2477 AN: 3466

East Asian (EAS) AF: 0.813 AC: 4210 AN: 5178

South Asian (SAS) AF: 0.528 AC: 2548 AN: 4824

European-Finnish (FIN) AF: 0.567 AC: 5991 AN: 10574

Middle Eastern (MID) AF: 0.735 AC: 216 AN: 294

European-Non Finnish (NFE) AF: 0.616 AC: 41866 AN: 67940

Other (OTH) AF: 0.631 AC: 1332 AN: 2110

Alfa AF: 0.580 Hom.: 3033

Bravo AF: 0.606

Asia WGS AF: 0.650 AC: 2255 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.6
DANN	Benign	0.84
PhyloP100		0.085
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs83921; hg19: chr9-33797056;