7-142252552-G-T

Variant names:

• chr7-142252552-G-T
• rs146814209
• NM_001001317.5:c.496C>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001001317.5(PRSS58):​c.496C>A​(p.Arg166Ser) 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. 17/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R166C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: PRSS58 NM_001001317.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.04
• Publications: 3 publications found

Genes affected

PRSS58 (HGNC:39125): (serine protease 58) This gene encodes a member of the trypsin family of serine proteases. This gene and several related trypsinogen genes are localized to the T cell receptor beta locus on chromosome 7. This gene was previously described as a trypsinogen-like pseudogene, but it is now thought to be a protein-coding gene. [provided by RefSeq, Jul 2008]

ENSG00000241881 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.28534955).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRSS58	NM_001001317.5	c.496C>A	p.Arg166Ser	missense_variant	Exon 5 of 6	ENST00000547058.6	NP_001001317.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRSS58	ENST00000547058.6	c.496C>A	p.Arg166Ser	missense_variant	Exon 5 of 6	1	NM_001001317.5	ENSP00000447588.2
PRSS58	ENST00000552471.1	c.496C>A	p.Arg166Ser	missense_variant	Exon 4 of 5	2		ENSP00000446916.1
ENSG00000241881	ENST00000486508.2	n.254+3769G>T		intron_variant	Intron 1 of 2	3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Benign	-0.051	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	16
DANN	Benign	0.93
DEOGEN2	Benign	0.25	T;T
Eigen	Benign	-0.21
Eigen_PC	Benign	-0.27
FATHMM_MKL	Benign	0.13	N
M_CAP	Benign	0.083	D
MetaRNN	Benign	0.29	T;T
MetaSVM	Benign	-0.34	T
MutationAssessor	Benign	0.78	N;N
PhyloP100		2.0
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-1.6	N;N
REVEL	Benign	0.20
Sift	Benign	0.28	T;T
Sift4G	Benign	0.072	T;T
Polyphen		0.84	P;P
Vest4		0.33
MutPred		0.37		Loss of catalytic residue at R166 (P = 0.005);Loss of catalytic residue at R166 (P = 0.005);
MVP		0.69
MPC		0.11
ClinPred		0.62	D
GERP RS		4.4
Varity_R		0.15
gMVP		0.44
Mutation Taster		=90/10	polymorphism

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: rs146814209; hg19: chr7-141952372; COSMIC: COSV101616130;