6-83517927-T-C

Variant names:

• chr6-83517927-T-C
• rs1171114
• NM_153362.3:c.-21+5233T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.657 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.-21+5233T>C		intron	N/A	NP_699193.2
	PRSS35	NM_001170423.2		c.-125-3608T>C		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.-21+5233T>C		intron	N/A	ENSP00000358714.3
	PRSS35	ENST00000867649.1		c.-125-3608T>C		intron	N/A	ENSP00000537708.1
	PRSS35	ENST00000867650.1		c.-426-3307T>C		intron	N/A	ENSP00000537709.1

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

African (AFR) AF: 0.597 AC: 24738 AN: 41420

American (AMR) AF: 0.668 AC: 10202 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.489 AC: 1694 AN: 3466

East Asian (EAS) AF: 0.637 AC: 3278 AN: 5146

South Asian (SAS) AF: 0.610 AC: 2934 AN: 4810

European-Finnish (FIN) AF: 0.608 AC: 6424 AN: 10564

Middle Eastern (MID) AF: 0.391 AC: 115 AN: 294

European-Non Finnish (NFE) AF: 0.567 AC: 38517 AN: 67962

Other (OTH) AF: 0.571 AC: 1201 AN: 2104

Alfa AF: 0.566 Hom.: 60308

Bravo AF: 0.590

Asia WGS AF: 0.660 AC: 2297 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.39
DANN	Benign	0.40
PhyloP100		-1.2
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: rs1171114; hg19: chr6-84227646; COSMIC: COSV63801150;