rs1171114

Positions:

• chr6-83517927-T-C
• chr6-83517927-T-G

Variant summary

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

The NM_153362.3(PRSS35):​c.-21+5233T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.589 in 151,954 control chromosomes in the GnomAD database, including 26,520 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 0.59 (26520 hom., cov: 32)
• Consequence: PRSS35 NM_153362.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.18

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.657 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRSS35	NM_153362.3	c.-21+5233T>C		intron_variant		ENST00000369700.4
PRSS35	NM_001170423.2	c.-125-3608T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRSS35	ENST00000369700.4	c.-21+5233T>C		intron_variant		1	NM_153362.3	P1

Frequencies

GnomAD3 genomes AF: 0.589 AC: 89413 AN: 151836 Hom.: 26475 Cov.: 32

Gnomad AFR AF: 0.598

Gnomad AMI AF: 0.451

Gnomad AMR AF: 0.667

Gnomad ASJ AF: 0.489

Gnomad EAS AF: 0.637

Gnomad SAS AF: 0.608

Gnomad FIN AF: 0.608

Gnomad MID AF: 0.380

Gnomad NFE AF: 0.567

Gnomad OTH AF: 0.565

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

GnomAD4 genome AF: 0.589 AC: 89514 AN: 151954 Hom.: 26520 Cov.: 32 AF XY: 0.592 AC XY: 43966 AN XY: 74276

Gnomad4 AFR AF: 0.597

Gnomad4 AMR AF: 0.668

Gnomad4 ASJ AF: 0.489

Gnomad4 EAS AF: 0.637

Gnomad4 SAS AF: 0.610

Gnomad4 FIN AF: 0.608

Gnomad4 NFE AF: 0.567

Gnomad4 OTH AF: 0.571

Alfa AF: 0.558 Hom.: 35445

Bravo AF: 0.590

Asia WGS AF: 0.660 AC: 2297 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.39
DANN	Benign	0.40

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: rs1171114; hg19: chr6-84227646; COSMIC: COSV63801150;