6-83516876-C-T

Variant summary

Our verdict is Benign. Variant got -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

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 = 0.857 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRSS35	NM_153362.3	c.-21+4182C>T		intron_variant		ENST00000369700.4
PRSS35	NM_001170423.2	c.-126+4182C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRSS35	ENST00000369700.4	c.-21+4182C>T		intron_variant		1	NM_153362.3	P1

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

Gnomad4 AFR AF: 0.764

Gnomad4 AMR AF: 0.776

Gnomad4 ASJ AF: 0.649

Gnomad4 EAS AF: 0.878

Gnomad4 SAS AF: 0.832

Gnomad4 FIN AF: 0.751

Gnomad4 NFE AF: 0.715

Gnomad4 OTH AF: 0.716

Alfa AF: 0.736 Hom.: 5308

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

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: rs1171113; hg19: chr6-84226595;