NM_013270.5:c.251C>G

Variant names:

• chr3-46717493-G-C
• rs758775351
• NM_013270.5:c.251C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_013270.5(PRSS50):​c.251C>G​(p.Ser84Trp) 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 1,461,748 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. S84L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: PRSS50 NM_013270.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.23

Genes affected

PRSS50 (HGNC:17910): (serine protease 50) Enables threonine-type endopeptidase activity. Involved in proteolysis. Located in endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000206549 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13379821).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRSS50	NM_013270.5	c.251C>G	p.Ser84Trp	missense_variant	Exon 2 of 6	ENST00000315170.13	NP_037402.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRSS50	ENST00000315170.13	c.251C>G	p.Ser84Trp	missense_variant	Exon 2 of 6	1	NM_013270.5	ENSP00000326598.7
ENSG00000206549	ENST00000460241.2	c.251C>G	p.Ser84Trp	missense_variant	Exon 7 of 11	2		ENSP00000418875.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461748 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727156

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53282

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1112008

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.055	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	0.42
DANN	Benign	0.82
DEOGEN2	Benign	0.0085	T;T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.016	N
LIST_S2	Benign	0.53	T;.
M_CAP	Benign	0.038	D
MetaRNN	Benign	0.13	T;T
MetaSVM	Uncertain	-0.16	T
MutationAssessor	Benign	0.69	N;N
PhyloP100		-4.2
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-1.4	N;N
REVEL	Uncertain	0.40
Sift	Benign	0.055	T;T
Sift4G	Uncertain	0.010	D;D
Polyphen		0.95	P;P
Vest4		0.25
MutPred		0.30		Loss of glycosylation at S84 (P = 0.0097);Loss of glycosylation at S84 (P = 0.0097);
MVP		0.23
MPC		0.39
ClinPred		0.35	T
GERP RS		-6.2
PromoterAI		-0.018	Neutral
Varity_R		0.059
gMVP		0.61
Mutation Taster		=98/2	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

Publications

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Other links and lift over

dbSNP: rs758775351; hg19: chr3-46758983;