rs7639979

Variant names:

• chr3-46733286-A-G
• rs7639979
• ENST00000460241.2:c.-542-13283T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000460241.2(ENSG00000206549):​c.-542-13283T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.228 in 152,106 control chromosomes in the GnomAD database, including 5,034 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 0.23 (5034 hom., cov: 32)
• Consequence: ENSG00000206549 ENST00000460241.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.52
• Publications: 6 publications found

Genes affected

ENSG00000206549 (HGNC:):

PRSS46P (HGNC:37325): (serine protease 46, pseudogene) Predicted to enable serine-type endopeptidase activity. Predicted to be involved in proteolysis. Predicted to be active in extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.403 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRSS46P	NR_147121.1	n.559+350T>C		intron_variant	Intron 3 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000206549	ENST00000460241.2	c.-542-13283T>C		intron_variant	Intron 4 of 10	2		ENSP00000418875.1
PRSS46P	ENST00000463091.2	n.561+350T>C		intron_variant	Intron 3 of 3	4
PRSS46P	ENST00000645911.2	n.520+350T>C		intron_variant	Intron 3 of 4

Frequencies

GnomAD3 genomes AF: 0.228 AC: 34591 AN: 151988 Hom.: 5027 Cov.: 32

Gnomad AFR AF: 0.408

Gnomad AMI AF: 0.234

Gnomad AMR AF: 0.193

Gnomad ASJ AF: 0.155

Gnomad EAS AF: 0.137

Gnomad SAS AF: 0.262

Gnomad FIN AF: 0.207

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.137

Gnomad OTH AF: 0.211

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

GnomAD4 genome AF: 0.228 AC: 34642 AN: 152106 Hom.: 5034 Cov.: 32 AF XY: 0.230 AC XY: 17073 AN XY: 74368

African (AFR) AF: 0.408 AC: 16930 AN: 41452

American (AMR) AF: 0.193 AC: 2956 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.155 AC: 538 AN: 3470

East Asian (EAS) AF: 0.137 AC: 709 AN: 5176

South Asian (SAS) AF: 0.261 AC: 1260 AN: 4822

European-Finnish (FIN) AF: 0.207 AC: 2195 AN: 10588

Middle Eastern (MID) AF: 0.211 AC: 62 AN: 294

European-Non Finnish (NFE) AF: 0.137 AC: 9334 AN: 67994

Other (OTH) AF: 0.211 AC: 445 AN: 2114

Alfa AF: 0.166 Hom.: 1442

Bravo AF: 0.237

Asia WGS AF: 0.191 AC: 666 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.031
DANN	Benign	0.39
PhyloP100		-1.5
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: rs7639979; hg19: chr3-46774776;