rs780015944

Variant names:

• chr7-142752957-A-C
• rs780015944
• NM_002769.5:c.681A>C

Your query was ambiguous. Multiple possible variants found:

• chr7-142752957-A-C
• chr7-142752957-A-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 2P and 14B. PM2 BP4_Strong BP6_Very_Strong BP7 BS2_Supporting

The NM_002769.5(PRSS1):​c.681A>C​(p.Gly227Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,848 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. G227G) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 28)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: PRSS1 NM_002769.5 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -5.49
• Publications: 0 publications found

Genes affected

PRSS1 (HGNC:9475): (serine protease 1) This gene encodes a trypsinogen, which is a member of the trypsin family of serine proteases. This enzyme is secreted by the pancreas and cleaved to its active form in the small intestine. It is active on peptide linkages involving the carboxyl group of lysine or arginine. Mutations in this gene are associated with hereditary pancreatitis. This gene and several other trypsinogen genes are localized to the T cell receptor beta locus on chromosome 7. [provided by RefSeq, Jul 2008]

PRSS1 Gene-Disease associations (from GenCC):

• hereditary chronic pancreatitis

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, ClinGen, PanelApp Australia, Illumina, Labcorp Genetics (formerly Invitae), Ambry Genetics
• malignant pancreatic neoplasm

  Inheritance: AD Classification: MODERATE Submitted by: Genomics England PanelApp

TRB (HGNC:12155):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BP6: Variant 7-142752957-A-C is Benign according to our data. Variant chr7-142752957-A-C is described in ClinVar as Likely_benign. ClinVar VariationId is 1159029.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-5.49 with no splicing effect.
• BS2: High AC in GnomAdExome4 at 5 AD gene. Variant has AC lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002769.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRSS1	NM_002769.5	MANE Select	c.681A>C	p.Gly227Gly	synonymous	Exon 5 of 5	NP_002760.1
	PRSS1	NR_172947.1		n.623A>C		non_coding_transcript_exon	Exon 5 of 5
	PRSS1	NR_172948.1		n.620A>C		non_coding_transcript_exon	Exon 5 of 5

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRSS1	ENST00000311737.12	TSL:1 MANE Select	c.681A>C	p.Gly227Gly	synonymous	Exon 5 of 5	ENSP00000308720.7
	PRSS1	ENST00000486171.5	TSL:5	c.723A>C	p.Gly241Gly	synonymous	Exon 6 of 6	ENSP00000417854.1
	PRSS1	ENST00000463701.1	TSL:2	n.1145A>C		non_coding_transcript_exon	Exon 3 of 3

Frequencies

GnomAD3 genomes Cov.: 28

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1461848 Hom.: 0 Cov.: 50 AF XY: 0.00000413 AC XY: 3 AN XY: 727236

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000450 AC: 5 AN: 1111968

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 28

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Hereditary pancreatitis (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	3.9
DANN	Benign	0.57
PhyloP100		-5.5

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

Other links and lift over

dbSNP: rs780015944; hg19: chr7-142460808;