rs3812141

chr6-83524425-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_153362.3(PRSS35):c.984C>T(p.Ser328=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.164 in 1,613,828 control chromosomes in the GnomAD database, including 23,057 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 0.18 (2691 hom., cov: 32)
  • Exomes 𝑓: 0.16 (20366 hom.)
• Consequence: PRSS35 NM_153362.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.34

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BP7: Synonymous conserved (PhyloP=-3.34 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.243 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRSS35	NM_153362.3	c.984C>T	p.Ser328=	synonymous_variant	2/2	ENST00000369700.4
PRSS35	NM_001170423.2	c.984C>T	p.Ser328=	synonymous_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRSS35	ENST00000369700.4	c.984C>T	p.Ser328=	synonymous_variant	2/2	1	NM_153362.3	P1

Frequencies

GnomAD3 genomes AF: 0.180 AC: 27278 AN: 151848 Hom.: 2689 Cov.: 32

Gnomad AFR AF: 0.247

Gnomad AMI AF: 0.194

Gnomad AMR AF: 0.121

Gnomad ASJ AF: 0.160

Gnomad EAS AF: 0.238

Gnomad SAS AF: 0.235

Gnomad FIN AF: 0.144

Gnomad MID AF: 0.160

Gnomad NFE AF: 0.150

Gnomad OTH AF: 0.168

GnomAD3 exomes AF: 0.168 AC: 42173 AN: 250956 Hom.: 3972 AF XY: 0.173 AC XY: 23446 AN XY: 135676

Gnomad AFR exome AF: 0.244

Gnomad AMR exome AF: 0.0843

Gnomad ASJ exome AF: 0.166

Gnomad EAS exome AF: 0.260

Gnomad SAS exome AF: 0.238

Gnomad FIN exome AF: 0.148

Gnomad NFE exome AF: 0.154

Gnomad OTH exome AF: 0.157

GnomAD4 exome AF: 0.163 AC: 237954 AN: 1461862 Hom.: 20366 Cov.: 36 AF XY: 0.165 AC XY: 120353 AN XY: 727232

Gnomad4 AFR exome AF: 0.251

Gnomad4 AMR exome AF: 0.0877

Gnomad4 ASJ exome AF: 0.165

Gnomad4 EAS exome AF: 0.270

Gnomad4 SAS exome AF: 0.238

Gnomad4 FIN exome AF: 0.154

Gnomad4 NFE exome AF: 0.154

Gnomad4 OTH exome AF: 0.166

GnomAD4 genome AF: 0.180 AC: 27282 AN: 151966 Hom.: 2691 Cov.: 32 AF XY: 0.181 AC XY: 13473 AN XY: 74286

Gnomad4 AFR AF: 0.247

Gnomad4 AMR AF: 0.121

Gnomad4 ASJ AF: 0.160

Gnomad4 EAS AF: 0.238

Gnomad4 SAS AF: 0.234

Gnomad4 FIN AF: 0.144

Gnomad4 NFE AF: 0.150

Gnomad4 OTH AF: 0.167

Alfa AF: 0.158 Hom.: 3389

Bravo AF: 0.177

Asia WGS AF: 0.180 AC: 623 AN: 3478

EpiCase AF: 0.151

EpiControl AF: 0.149

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
Cadd	Benign	0.22
Dann	Benign	0.75

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: rs3812141; hg19: chr6-84234144; COSMIC: COSV63800655;