6-83516876-C-T

Variant names:

• chr6-83516876-C-T
• rs1171113
• NM_153362.3:c.-21+4182C>T

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+4182C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.744 in 152,012 control chromosomes in the GnomAD database, including 42,280 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 0.74 (42280 hom., cov: 31)
• Consequence: PRSS35 NM_153362.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.950
• Publications: 13 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 = 0.857 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRSS35	NM_153362.3	c.-21+4182C>T		intron_variant	Intron 1 of 1	ENST00000369700.4	NP_699193.2
PRSS35	NM_001170423.2	c.-126+4182C>T		intron_variant	Intron 1 of 2		NP_001163894.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRSS35	ENST00000369700.4	c.-21+4182C>T		intron_variant	Intron 1 of 1	1	NM_153362.3	ENSP00000358714.3

Frequencies

GnomAD3 genomes AF: 0.744 AC: 113002 AN: 151894 Hom.: 42226 Cov.: 31

Gnomad AFR AF: 0.764

Gnomad AMI AF: 0.647

Gnomad AMR AF: 0.776

Gnomad ASJ AF: 0.649

Gnomad EAS AF: 0.878

Gnomad SAS AF: 0.830

Gnomad FIN AF: 0.751

Gnomad MID AF: 0.532

Gnomad NFE AF: 0.715

Gnomad OTH AF: 0.711

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

GnomAD4 genome AF: 0.744 AC: 113112 AN: 152012 Hom.: 42280 Cov.: 31 AF XY: 0.748 AC XY: 55608 AN XY: 74298

African (AFR) AF: 0.764 AC: 31671 AN: 41464

American (AMR) AF: 0.776 AC: 11864 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.649 AC: 2251 AN: 3468

East Asian (EAS) AF: 0.878 AC: 4527 AN: 5156

South Asian (SAS) AF: 0.832 AC: 4003 AN: 4812

European-Finnish (FIN) AF: 0.751 AC: 7922 AN: 10552

Middle Eastern (MID) AF: 0.548 AC: 161 AN: 294

European-Non Finnish (NFE) AF: 0.715 AC: 48610 AN: 67952

Other (OTH) AF: 0.716 AC: 1513 AN: 2112

Alfa AF: 0.747 Hom.: 16006

Bravo AF: 0.742

Asia WGS AF: 0.835 AC: 2903 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	0.049
DANN	Benign	0.55
PhyloP100		-0.95
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: rs1171113; hg19: chr6-84226595;