NM_001001317.5:c.718A>C

Variant names:

• chr7-142252229-T-G
• rs1798477521
• NM_001001317.5:c.718A>C

Variant summary

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

The NM_001001317.5(PRSS58):​c.718A>C​(p.Asn240His) 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. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: PRSS58 NM_001001317.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.520
• 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=0.2811757).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRSS58	NM_001001317.5	c.718A>C	p.Asn240His	missense_variant	Exon 6 of 6	ENST00000547058.6	NP_001001317.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRSS58	ENST00000547058.6	c.718A>C	p.Asn240His	missense_variant	Exon 6 of 6	1	NM_001001317.5	ENSP00000447588.2
PRSS58	ENST00000552471.1	c.718A>C	p.Asn240His	missense_variant	Exon 5 of 5	2		ENSP00000446916.1
ENSG00000241881	ENST00000486508.2	n.254+3446T>G		intron_variant	Intron 1 of 2	3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 22, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.718A>C (p.N240H) alteration is located in exon 6 (coding exon 5) of the PRSS58 gene. This alteration results from a A to C substitution at nucleotide position 718, causing the asparagine (N) at amino acid position 240 to be replaced by a histidine (H). 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	Benign	0.13
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.045	T;T
Eigen	Benign	-0.41
Eigen_PC	Benign	-0.58
FATHMM_MKL	Benign	0.093	N
M_CAP	Uncertain	0.10	D
MetaRNN	Benign	0.28	T;T
MetaSVM	Benign	-0.59	T
MutationAssessor	Benign	1.3	L;L
PhyloP100		0.52
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-2.2	N;N
REVEL	Benign	0.28
Sift	Benign	0.12	T;T
Sift4G	Benign	0.091	T;T
Polyphen		0.95	P;P
Vest4		0.26
MutPred		0.28		Gain of catalytic residue at I238 (P = 0.1302);Gain of catalytic residue at I238 (P = 0.1302);
MVP		0.71
MPC		0.20
ClinPred		0.46	T
GERP RS		1.1
Varity_R		0.035
gMVP		0.43
Mutation Taster		=91/9	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: rs1798477521; hg19: chr7-141952049;