rs512140

Positions:

• chr6-83520934-A-G

Variant summary

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

The NM_153362.3(PRSS35):​c.-20-2488A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.77 in 152,020 control chromosomes in the GnomAD database, including 45,495 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 0.77 (45495 hom., cov: 31)
• Consequence: PRSS35 NM_153362.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.242

Genes affected

PRSS35 (HGNC:21387): (serine protease 35) Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.858 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRSS35	NM_153362.3	c.-20-2488A>G		intron_variant		ENST00000369700.4	NP_699193.2
PRSS35	NM_001170423.2	c.-125-601A>G		intron_variant			NP_001163894.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRSS35	ENST00000369700.4	c.-20-2488A>G		intron_variant		1	NM_153362.3	ENSP00000358714	P1

Frequencies

GnomAD3 genomes AF: 0.770 AC: 116916 AN: 151904 Hom.: 45419 Cov.: 31

Gnomad AFR AF: 0.855

Gnomad AMI AF: 0.646

Gnomad AMR AF: 0.786

Gnomad ASJ AF: 0.647

Gnomad EAS AF: 0.879

Gnomad SAS AF: 0.829

Gnomad FIN AF: 0.750

Gnomad MID AF: 0.528

Gnomad NFE AF: 0.715

Gnomad OTH AF: 0.730

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

GnomAD4 genome AF: 0.770 AC: 117053 AN: 152020 Hom.: 45495 Cov.: 31 AF XY: 0.774 AC XY: 57479 AN XY: 74302

Gnomad4 AFR AF: 0.855

Gnomad4 AMR AF: 0.786

Gnomad4 ASJ AF: 0.647

Gnomad4 EAS AF: 0.879

Gnomad4 SAS AF: 0.831

Gnomad4 FIN AF: 0.750

Gnomad4 NFE AF: 0.715

Gnomad4 OTH AF: 0.735

Alfa AF: 0.752 Hom.: 6873

Bravo AF: 0.771

Asia WGS AF: 0.842 AC: 2929 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.8
DANN	Benign	0.33

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: rs512140; hg19: chr6-84230653;