6-83524455-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Moderate BP6_Moderate BP7 BA1

The NM_153362.3(PRSS35):c.1014C>T(p.Tyr338=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00496 in 1,614,100 control chromosomes in the GnomAD database, including 347 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.027 (191 hom., cov: 32)
  • Exomes 𝑓: 0.0026 (156 hom.)
• Consequence: PRSS35 NM_153362.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.293

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=-0.43).
• BP6: Variant 6-83524455-C-T is Benign according to our data. Variant chr6-83524455-C-T is described in ClinVar as [Benign]. Clinvar id is 785175.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.293 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0924 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRSS35	NM_153362.3	c.1014C>T	p.Tyr338=	synonymous_variant	2/2	ENST00000369700.4
PRSS35	NM_001170423.2	c.1014C>T	p.Tyr338=	synonymous_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRSS35	ENST00000369700.4	c.1014C>T	p.Tyr338=	synonymous_variant	2/2	1	NM_153362.3	P1

Frequencies

GnomAD3 genomes AF: 0.0274 AC: 4172 AN: 152094 Hom.: 191 Cov.: 32

Gnomad AFR AF: 0.0951

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0110

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000235

Gnomad OTH AF: 0.0230

GnomAD3 exomes AF: 0.00683 AC: 1716 AN: 251206 Hom.: 66 AF XY: 0.00521 AC XY: 708 AN XY: 135774

Gnomad AFR exome AF: 0.0932

Gnomad AMR exome AF: 0.00463

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000163

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000211

Gnomad OTH exome AF: 0.00212

GnomAD4 exome AF: 0.00262 AC: 3830 AN: 1461888 Hom.: 156 Cov.: 34 AF XY: 0.00230 AC XY: 1674 AN XY: 727246

Gnomad4 AFR exome AF: 0.0938

Gnomad4 AMR exome AF: 0.00470

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000243

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000863

Gnomad4 OTH exome AF: 0.00558

GnomAD4 genome AF: 0.0274 AC: 4173 AN: 152212 Hom.: 191 Cov.: 32 AF XY: 0.0270 AC XY: 2007 AN XY: 74416

Gnomad4 AFR AF: 0.0948

Gnomad4 AMR AF: 0.0110

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000235

Gnomad4 OTH AF: 0.0227

Alfa AF: 0.0107 Hom.: 35

Bravo AF: 0.0297

Asia WGS AF: 0.00404 AC: 14 AN: 3478

EpiCase AF: 0.000273

EpiControl AF: 0.000474

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jun 04, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
Cadd	Benign	1.6
Dann	Benign	0.68

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: rs57628521; hg19: chr6-84234174;