7-142752462-T-C

Variant names:

• chr7-142752462-T-C
• rs6666
• NM_002769.5:c.486T>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6_Very_Strong BP7

The NM_002769.5(PRSS1):​c.486T>C​(p.Asp162Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.43 (1831 hom., cov: 36)
  • Exomes 𝑓: 0.40 (15706 hom.)
  • Failed GnomAD Quality Control
• Consequence: PRSS1 NM_002769.5 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:11
• Conservation: PhyloP100: -3.83
• Publications: 29 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: Illumina, Orphanet, Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics, PanelApp Australia
• malignant pancreatic neoplasm

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

TRB (HGNC:12155):

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 7-142752462-T-C is Benign according to our data. Variant chr7-142752462-T-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 239391.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-3.83 with no splicing effect.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRSS1	NM_002769.5	MANE Select	c.486T>C	p.Asp162Asp	synonymous	Exon 4 of 5	NP_002760.1	P07477
	PRSS1	NR_172947.1		n.428T>C		non_coding_transcript_exon	Exon 4 of 5
	PRSS1	NR_172948.1		n.425T>C		non_coding_transcript_exon	Exon 4 of 5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRSS1	ENST00000311737.12	TSL:1 MANE Select	c.486T>C	p.Asp162Asp	synonymous	Exon 4 of 5	ENSP00000308720.7	P07477
	PRSS1	ENST00000486171.5	TSL:5	c.528T>C	p.Asp176Asp	synonymous	Exon 5 of 6	ENSP00000417854.1	E7EQ64
	PRSS1	ENST00000492062.2	TSL:2	c.486T>C	p.Asp162Asp	synonymous	Exon 4 of 5	ENSP00000419912.2	H0Y8D1

Frequencies

GnomAD3 genomes AF: 0.427 AC: 63245 AN: 148028 Hom.: 1829 Cov.: 36

Gnomad AFR AF: 0.517

Gnomad AMI AF: 0.382

Gnomad AMR AF: 0.422

Gnomad ASJ AF: 0.409

Gnomad EAS AF: 0.197

Gnomad SAS AF: 0.259

Gnomad FIN AF: 0.421

Gnomad MID AF: 0.327

Gnomad NFE AF: 0.410

Gnomad OTH AF: 0.424

GnomAD2 exomes AF: 0.385 AC: 96253 AN: 249982 AF XY: 0.380

Gnomad AFR exome AF: 0.360

Gnomad AMR exome AF: 0.429

Gnomad ASJ exome AF: 0.414

Gnomad EAS exome AF: 0.208

Gnomad FIN exome AF: 0.425

Gnomad NFE exome AF: 0.426

Gnomad OTH exome AF: 0.412

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.405 AC: 585672 AN: 1447336 Hom.: 15706 Cov.: 69 AF XY: 0.400 AC XY: 288125 AN XY: 720822

African (AFR) AF: 0.452 AC: 13721 AN: 30362

American (AMR) AF: 0.413 AC: 18333 AN: 44348

Ashkenazi Jewish (ASJ) AF: 0.410 AC: 10669 AN: 26028

East Asian (EAS) AF: 0.217 AC: 8608 AN: 39672

South Asian (SAS) AF: 0.263 AC: 22665 AN: 86116

European-Finnish (FIN) AF: 0.426 AC: 22684 AN: 53306

Middle Eastern (MID) AF: 0.353 AC: 2005 AN: 5682

European-Non Finnish (NFE) AF: 0.421 AC: 463854 AN: 1102128

Other (OTH) AF: 0.388 AC: 23133 AN: 59694

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.427 AC: 63305 AN: 148142 Hom.: 1831 Cov.: 36 AF XY: 0.424 AC XY: 30713 AN XY: 72506

African (AFR) AF: 0.517 AC: 19933 AN: 38540

American (AMR) AF: 0.422 AC: 6339 AN: 15030

Ashkenazi Jewish (ASJ) AF: 0.409 AC: 1409 AN: 3442

East Asian (EAS) AF: 0.198 AC: 1015 AN: 5138

South Asian (SAS) AF: 0.259 AC: 1228 AN: 4742

European-Finnish (FIN) AF: 0.421 AC: 4408 AN: 10458

Middle Eastern (MID) AF: 0.331 AC: 96 AN: 290

European-Non Finnish (NFE) AF: 0.410 AC: 27670 AN: 67554

Other (OTH) AF: 0.421 AC: 862 AN: 2046

Alfa AF: 0.378 Hom.: 366

Asia WGS AF: 0.273 AC: 956 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	5	Hereditary pancreatitis (5)
-	-	5	not specified (5)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.12
DANN	Benign	0.20
PhyloP100		-3.8
Mutation Taster		=99/1	polymorphism (auto)

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: rs6666; hg19: chr7-142460313; COSMIC: COSV61190814; COSMIC: COSV61190814;