chr7-142749500-A-G

Position:

• chr7-142749500-A-G

Variant summary

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

The NM_002769.5(PRSS1):​c.16A>G​(p.Ile6Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I6F) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 34)
• Consequence: PRSS1 NM_002769.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.718

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]

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=0.15418038).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRSS1	NM_002769.5	c.16A>G	p.Ile6Val	missense_variant	1/5	ENST00000311737.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRSS1	ENST00000311737.12	c.16A>G	p.Ile6Val	missense_variant	1/5	1	NM_002769.5	P1
PRSS1	ENST00000486171.5	c.16A>G	p.Ile6Val	missense_variant	1/6	5
PRSS1	ENST00000485223.1	n.29A>G		non_coding_transcript_exon_variant	1/2	2
PRSS1	ENST00000497041.1	n.20A>G		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 46

GnomAD4 genome Cov.: 34

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Hereditary pancreatitis Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 03, 2023

The p.I6V variant (also known as c.16A>G), located in coding exon 1 of the PRSS1 gene, results from an A to G substitution at nucleotide position 16. The isoleucine at codon 6 is replaced by valine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	12
DANN	Benign	0.50
DEOGEN2	Benign	0.23	.;.;T
Eigen	Benign	-0.69
Eigen_PC	Benign	-0.65
FATHMM_MKL	Benign	0.49	N
M_CAP	Benign	0.029	D
MetaRNN	Benign	0.15	T;T;T
MetaSVM	Benign	-0.74	T
MutationAssessor	Benign	-0.65	.;.;N
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-0.64	N;.;N
REVEL	Benign	0.12
Sift	Benign	0.44	T;.;T
Sift4G	Benign	0.56	T;T;T
Polyphen		0.0020	.;.;B
Vest4		0.14
MutPred		0.47		Loss of helix (P = 0.0167);Loss of helix (P = 0.0167);Loss of helix (P = 0.0167);
MVP		0.61
MPC		0.14
ClinPred		0.28	T
GERP RS		0.65
Varity_R		0.016
gMVP		0.59

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-142457351;