rs11859950

Variant names:

• chr16-58284679-C-A
• rs11859950
• NM_001305173.2:c.565G>T

Your query was ambiguous. Multiple possible variants found:

• chr16-58284679-C-A
• chr16-58284679-C-G
• chr16-58284679-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001305173.2(PRSS54):​c.565G>T​(p.Val189Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,826 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: PRSS54 NM_001305173.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.99

Genes affected

PRSS54 (HGNC:26336): (serine protease 54) This gene encodes a putative serine-type endopeptidase containing the peptidase S1 domain. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Feb 2015]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.768

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRSS54	NM_001305173.2	c.565G>T	p.Val189Leu	missense_variant	Exon 6 of 7	ENST00000567164.6	NP_001292102.1
PRSS54	NM_001080492.2	c.565G>T	p.Val189Leu	missense_variant	Exon 6 of 7		NP_001073961.1
PRSS54	NM_001305174.2	c.268G>T	p.Val90Leu	missense_variant	Exon 5 of 6		NP_001292103.1
PRSS54	XM_047433779.1	c.31G>T	p.Val11Leu	missense_variant	Exon 2 of 3		XP_047289735.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRSS54	ENST00000567164.6	c.565G>T	p.Val189Leu	missense_variant	Exon 6 of 7	1	NM_001305173.2	ENSP00000455024.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251478 Hom.: 0 AF XY: 0.00000736 AC XY: 1 AN XY: 135912

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000879

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461826 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727212

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 31

Alfa AF: 0.0000243 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.41
BayesDel_addAF	Uncertain	0.078	D
BayesDel_noAF	Benign	-0.13
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.15	T;T;.;.
Eigen	Benign	0.15
Eigen_PC	Benign	0.13
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.77	.;T;T;T
M_CAP	Uncertain	0.14	D
MetaRNN	Pathogenic	0.77	D;D;D;D
MetaSVM	Uncertain	0.22	D
MutationAssessor	Benign	1.8	L;L;.;.
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-1.2	N;N;N;N
REVEL	Uncertain	0.44
Sift	Uncertain	0.020	D;D;T;D
Sift4G	Uncertain	0.056	T;T;T;.
Polyphen		0.96	D;D;.;.
Vest4		0.50
MutPred		0.76		Loss of methylation at K186 (P = 0.0928);Loss of methylation at K186 (P = 0.0928);.;.;
MVP		0.86
MPC		0.60
ClinPred		0.88	D
GERP RS		3.9
Varity_R		0.23
gMVP		0.64

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs11859950; hg19: chr16-58318583;