6-83524266-T-C

Position:

• chr6-83524266-T-C

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_153362.3(PRSS35):​c.825T>C​(p.Tyr275=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00631 in 1,614,134 control chromosomes in the GnomAD database, including 48 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0041 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0065 (46 hom.)
• Consequence: PRSS35 NM_153362.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.884

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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP6: Variant 6-83524266-T-C is Benign according to our data. Variant chr6-83524266-T-C is described in ClinVar as [Benign]. Clinvar id is 720305.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.884 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRSS35	NM_153362.3	c.825T>C	p.Tyr275=	synonymous_variant	2/2	ENST00000369700.4	NP_699193.2
PRSS35	NM_001170423.2	c.825T>C	p.Tyr275=	synonymous_variant	3/3		NP_001163894.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRSS35	ENST00000369700.4	c.825T>C	p.Tyr275=	synonymous_variant	2/2	1	NM_153362.3	ENSP00000358714	P1

Frequencies

GnomAD3 genomes AF: 0.00410 AC: 624 AN: 152128 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.00159

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00347

Gnomad ASJ AF: 0.00576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000622

Gnomad FIN AF: 0.00283

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.00647

Gnomad OTH AF: 0.00287

GnomAD3 exomes AF: 0.00423 AC: 1063 AN: 251384 Hom.: 6 AF XY: 0.00441 AC XY: 599 AN XY: 135866

Gnomad AFR exome AF: 0.00117

Gnomad AMR exome AF: 0.00234

Gnomad ASJ exome AF: 0.00665

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.00111

Gnomad FIN exome AF: 0.00305

Gnomad NFE exome AF: 0.00678

Gnomad OTH exome AF: 0.00391

GnomAD4 exome AF: 0.00654 AC: 9567 AN: 1461888 Hom.: 46 Cov.: 36 AF XY: 0.00641 AC XY: 4664 AN XY: 727244

Gnomad4 AFR exome AF: 0.00119

Gnomad4 AMR exome AF: 0.00235

Gnomad4 ASJ exome AF: 0.00650

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00103

Gnomad4 FIN exome AF: 0.00333

Gnomad4 NFE exome AF: 0.00775

Gnomad4 OTH exome AF: 0.00591

GnomAD4 genome AF: 0.00410 AC: 624 AN: 152246 Hom.: 2 Cov.: 32 AF XY: 0.00371 AC XY: 276 AN XY: 74436

Gnomad4 AFR AF: 0.00159

Gnomad4 AMR AF: 0.00347

Gnomad4 ASJ AF: 0.00576

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000623

Gnomad4 FIN AF: 0.00283

Gnomad4 NFE AF: 0.00647

Gnomad4 OTH AF: 0.00284

Alfa AF: 0.00614 Hom.: 3

Bravo AF: 0.00418

EpiCase AF: 0.00687

EpiControl AF: 0.00682

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

Labcorp Genetics (formerly Invitae), Labcorp

Apr 10, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	0.061
DANN	Benign	0.44

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: rs146852080; hg19: chr6-84233985;