7-142751934-G-T

Variant names:

• chr7-142751934-G-T
• rs199422123
• NM_002769.5:c.361G>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 4P and 4B. PM1 PM2 BP4_Strong

The NM_002769.5(PRSS1):​c.361G>T​(p.Ala121Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,880 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: PRSS1 NM_002769.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.95

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]

TRB (HGNC:12155):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM1: In a strand (size 2) in uniprot entity TRY1_HUMAN there are 6 pathogenic changes around while only 0 benign (100%) in NM_002769.5
• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06716621).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRSS1	NM_002769.5	c.361G>T	p.Ala121Ser	missense_variant	Exon 3 of 5	ENST00000311737.12	NP_002760.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRSS1	ENST00000311737.12	c.361G>T	p.Ala121Ser	missense_variant	Exon 3 of 5	1	NM_002769.5	ENSP00000308720.7

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461880 Hom.: 0 Cov.: 61 AF XY: 0.00000138 AC XY: 1 AN XY: 727242

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

Alfa AF: 0.0000689 Hom.: 0

ExAC AF: 0.0000659 AC: 8

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.061
BayesDel_addAF	Benign	-0.043	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	0.0020
DANN	Benign	0.18
DEOGEN2	Benign	0.31	.;.;T;T
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.011	N
M_CAP	Uncertain	0.13	D
MetaRNN	Benign	0.067	T;T;T;T
MetaSVM	Benign	-0.50	T
MutationAssessor	Benign	-0.41	.;.;N;.
PrimateAI	Benign	0.28	T
PROVEAN	Benign	0.79	N;.;N;N
REVEL	Uncertain	0.34
Sift	Benign	1.0	T;.;T;T
Sift4G	Benign	1.0	T;T;T;T
Polyphen		0.0	B;.;B;.
Vest4		0.24
MutPred		0.39		Gain of catalytic residue at A135 (P = 0.0394);.;.;.;
MVP		0.46
MPC		0.15
ClinPred		0.070	T
GERP RS		-6.6
Varity_R		0.19
gMVP		0.41

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs199422123; hg19: chr7-142459785;