rs6499946

chr16-58292706-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001305173.2(PRSS54):c.85+1026C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.788 in 152,170 control chromosomes in the GnomAD database, including 47,977 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.79 (47977 hom., cov: 32)
• Consequence: PRSS54 NM_001305173.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.313

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.9 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRSS54	NM_001305173.2	c.85+1026C>A		intron_variant		ENST00000567164.6
PRSS54	NM_001080492.2	c.85+1026C>A		intron_variant
PRSS54	NM_001305174.2	c.-35+1026C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRSS54	ENST00000567164.6	c.85+1026C>A		intron_variant		1	NM_001305173.2	P1

Frequencies

GnomAD3 genomes AF: 0.788 AC: 119875 AN: 152052 Hom.: 47930 Cov.: 32

Gnomad AFR AF: 0.908

Gnomad AMI AF: 0.852

Gnomad AMR AF: 0.660

Gnomad ASJ AF: 0.739

Gnomad EAS AF: 0.591

Gnomad SAS AF: 0.617

Gnomad FIN AF: 0.792

Gnomad MID AF: 0.639

Gnomad NFE AF: 0.775

Gnomad OTH AF: 0.748

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.788 AC: 119977 AN: 152170 Hom.: 47977 Cov.: 32 AF XY: 0.781 AC XY: 58094 AN XY: 74380

Gnomad4 AFR AF: 0.908

Gnomad4 AMR AF: 0.660

Gnomad4 ASJ AF: 0.739

Gnomad4 EAS AF: 0.590

Gnomad4 SAS AF: 0.618

Gnomad4 FIN AF: 0.792

Gnomad4 NFE AF: 0.775

Gnomad4 OTH AF: 0.743

Alfa AF: 0.776 Hom.: 7831

Bravo AF: 0.783

Asia WGS AF: 0.630 AC: 2196 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	1.5
Dann	Benign	0.52

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

LitVar

Other links and lift over

dbSNP: rs6499946; hg19: chr16-58326610;