rs512140

Variant names:

• chr6-83520934-A-G
• rs512140
• NM_153362.3:c.-20-2488A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153362.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRSS35	NM_153362.3	MANE Select	c.-20-2488A>G		intron	N/A	NP_699193.2
	PRSS35	NM_001170423.2		c.-125-601A>G		intron	N/A	NP_001163894.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRSS35	ENST00000369700.4	TSL:1 MANE Select	c.-20-2488A>G		intron	N/A	ENSP00000358714.3
	PRSS35	ENST00000867649.1		c.-125-601A>G		intron	N/A	ENSP00000537708.1
	PRSS35	ENST00000867650.1		c.-426-300A>G		intron	N/A	ENSP00000537709.1

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

African (AFR) AF: 0.855 AC: 35464 AN: 41468

American (AMR) AF: 0.786 AC: 12016 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.647 AC: 2246 AN: 3470

East Asian (EAS) AF: 0.879 AC: 4535 AN: 5160

South Asian (SAS) AF: 0.831 AC: 4000 AN: 4814

European-Finnish (FIN) AF: 0.750 AC: 7921 AN: 10560

Middle Eastern (MID) AF: 0.544 AC: 160 AN: 294

European-Non Finnish (NFE) AF: 0.715 AC: 48573 AN: 67956

Other (OTH) AF: 0.735 AC: 1550 AN: 2110

Alfa AF: 0.780 Hom.: 19384

Bravo AF: 0.771

Asia WGS AF: 0.842 AC: 2929 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.8
DANN	Benign	0.33
PhyloP100		-0.24
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: rs512140; hg19: chr6-84230653;