7-142255301-C-A

Variant names:

• chr7-142255301-C-A
• rs1370923240
• NM_001001317.5:c.190G>T

Variant summary

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

The NM_001001317.5(PRSS58):​c.190G>T​(p.Val64Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,418 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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. V64M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: PRSS58 NM_001001317.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.52
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.32820308).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRSS58	NM_001001317.5	c.190G>T	p.Val64Leu	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.190G>T	p.Val64Leu	missense_variant	Exon 4 of 6	1	NM_001001317.5	ENSP00000447588.2
PRSS58	ENST00000552471.1	c.190G>T	p.Val64Leu	missense_variant	Exon 3 of 5	2		ENSP00000446916.1
ENSG00000241881	ENST00000486508.2	n.254+6518C>A		intron_variant	Intron 1 of 2	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461418 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 726958

African (AFR) AF: 0.00 AC: 0 AN: 33456

American (AMR) AF: 0.00 AC: 0 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26126

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39684

South Asian (SAS) AF: 0.00 AC: 0 AN: 86236

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53392

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111660

Other (OTH) AF: 0.00 AC: 0 AN: 60390

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Benign	-0.068	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	14
DANN	Benign	0.91
DEOGEN2	Uncertain	0.45	T;T
Eigen	Benign	-0.70
Eigen_PC	Benign	-0.73
FATHMM_MKL	Benign	0.33	N
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.33	T;T
MetaSVM	Benign	-0.34	T
MutationAssessor	Uncertain	2.3	M;M
PhyloP100		2.5
PrimateAI	Benign	0.47	T
PROVEAN	Uncertain	-2.5	D;D
REVEL	Benign	0.21
Sift	Benign	0.054	T;T
Sift4G	Benign	0.14	T;T
Polyphen		0.070	B;B
Vest4		0.12
MutPred		0.64		Loss of methylation at K61 (P = 0.0752);Loss of methylation at K61 (P = 0.0752);
MVP		0.57
MPC		0.037
ClinPred		0.13	T
GERP RS		1.7
Varity_R		0.055
gMVP		0.44
Mutation Taster		=85/15	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1370923240; hg19: chr7-141955121;