rs6499946

Variant names:

• chr16-58292706-G-T
• rs6499946
• NM_001305173.2:c.85+1026C>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
PRSS54	NM_001305173.2	c.85+1026C>A		intron_variant	Intron 3 of 6	ENST00000567164.6	NP_001292102.1
PRSS54	NM_001080492.2	c.85+1026C>A		intron_variant	Intron 3 of 6		NP_001073961.1
PRSS54	NM_001305174.2	c.-35+1026C>A		intron_variant	Intron 3 of 5		NP_001292103.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRSS54	ENST00000567164.6	c.85+1026C>A		intron_variant	Intron 3 of 6	1	NM_001305173.2	ENSP00000455024.1

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

African (AFR) AF: 0.908 AC: 37721 AN: 41538

American (AMR) AF: 0.660 AC: 10081 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.739 AC: 2565 AN: 3472

East Asian (EAS) AF: 0.590 AC: 3030 AN: 5134

South Asian (SAS) AF: 0.618 AC: 2982 AN: 4828

European-Finnish (FIN) AF: 0.792 AC: 8394 AN: 10592

Middle Eastern (MID) AF: 0.619 AC: 182 AN: 294

European-Non Finnish (NFE) AF: 0.775 AC: 52676 AN: 68008

Other (OTH) AF: 0.743 AC: 1571 AN: 2114

Alfa AF: 0.779 Hom.: 8142

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
PhyloP100		0.31
Mutation Taster		=100/0	polymorphism (auto)

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: rs6499946; hg19: chr16-58326610;