chr7-142255081-G-A

Variant names:

• chr7-142255081-G-A
• NM_001001317.5:c.410C>T

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001001317.5(PRSS58):​c.410C>T​(p.Thr137Ile) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PRSS58 NM_001001317.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.32
• Publications: 0 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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.908

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRSS58	NM_001001317.5	c.410C>T	p.Thr137Ile	missense_variant	Exon 4 of 6	ENST00000547058.6	NP_001001317.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRSS58	ENST00000547058.6	c.410C>T	p.Thr137Ile	missense_variant	Exon 4 of 6	1	NM_001001317.5	ENSP00000447588.2
PRSS58	ENST00000552471.1	c.410C>T	p.Thr137Ile	missense_variant	Exon 3 of 5	2		ENSP00000446916.1
ENSG00000241881	ENST00000486508.2	n.254+6298G>A		intron_variant	Intron 1 of 2	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 06, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.410C>T (p.T137I) alteration is located in exon 4 (coding exon 3) of the PRSS58 gene. This alteration results from a C to T substitution at nucleotide position 410, causing the threonine (T) at amino acid position 137 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.75
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.040
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.50	T;T
Eigen	Uncertain	0.57
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Uncertain	0.83	D
M_CAP	Benign	0.078	D
MetaRNN	Pathogenic	0.91	D;D
MetaSVM	Uncertain	0.26	D
MutationAssessor	Uncertain	2.9	M;M
PhyloP100		4.3
PrimateAI	Uncertain	0.57	T
PROVEAN	Uncertain	-3.3	D;D
REVEL	Uncertain	0.52
Sift	Uncertain	0.0010	D;D
Sift4G	Benign	0.080	T;T
Polyphen		1.0	D;D
Vest4		0.68
MutPred		0.75		Gain of sheet (P = 0.1208);Gain of sheet (P = 0.1208);
MVP		0.81
MPC		0.24
ClinPred		0.98	D
GERP RS		4.0
Varity_R		0.32
gMVP		0.73
Mutation Taster		=78/22	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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

hg19: chr7-141954901;