Variant 6-83523633-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_153362.3(PRSS35):c.192C>A(p.Ile64=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00173 in 1,614,086 control chromosomes in the GnomAD database, including 27 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0056 ( 11 hom., cov: 32)

Exomes 𝑓: 0.0013 ( 16 hom. )

Consequence

PRSS35
NM_153362.3 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.679

Variant links:

Genes affected

PRSS35 (HGNC:21387): (serine protease 35) Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

PRSS35 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.48).

BP6

Variant 6-83523633-C-A is Benign according to our data. Variant chr6-83523633-C-A is described in ClinVar as [Benign]. Clinvar id is 728225.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.679 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00562 (856/152232) while in subpopulation AFR AF= 0.017 (705/41530). AF 95% confidence interval is 0.0159. There are 11 homozygotes in gnomad4. There are 376 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 11 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRSS35	NM_153362.3 linkuse as main transcript	c.192C>A	p.Ile64=	synonymous_variant	2/2	ENST00000369700.4	NP_699193.2
PRSS35	NM_001170423.2 linkuse as main transcript	c.192C>A	p.Ile64=	synonymous_variant	3/3		NP_001163894.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRSS35	ENST00000369700.4 linkuse as main transcript	c.192C>A	p.Ile64=	synonymous_variant	2/2	1	NM_153362.3	ENSP00000358714	P1

Frequencies

GnomAD3 genomes

AF:

0.00557

AC:

848

AN:

152114

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0168

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00419

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.000189

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000985

Gnomad OTH

AF:

0.00669

GnomAD3 exomes

AF:

0.00220

AC:

552

AN:

251294

Hom.:

AF XY:

0.00191

AC XY:

259

AN XY:

135802

show subpopulations

Gnomad AFR exome

AF:

0.0165

Gnomad AMR exome

AF:

0.00275

Gnomad ASJ exome

AF:

0.000199

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.000621

Gnomad FIN exome

AF:

0.000231

Gnomad NFE exome

AF:

0.00126

Gnomad OTH exome

AF:

0.00294

GnomAD4 exome

AF:

0.00132

AC:

1930

AN:

1461854

Hom.:

Cov.:

AF XY:

0.00135

AC XY:

984

AN XY:

727224

show subpopulations

Gnomad4 AFR exome

AF:

0.0189

Gnomad4 AMR exome

AF:

0.00262

Gnomad4 ASJ exome

AF:

0.000191

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.000638

Gnomad4 FIN exome

AF:

0.000243

Gnomad4 NFE exome

AF:

0.000713

Gnomad4 OTH exome

AF:

0.00333

GnomAD4 genome

AF:

0.00562

AC:

856

AN:

152232

Hom.:

Cov.:

AF XY:

0.00505

AC XY:

376

AN XY:

74440

show subpopulations

Gnomad4 AFR

AF:

0.0170

Gnomad4 AMR

AF:

0.00418

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.000189

Gnomad4 NFE

AF:

0.000985

Gnomad4 OTH

AF:

0.00662

Alfa

AF:

0.00424

Hom.:

Bravo

AF:

0.00635

Asia WGS

AF:

0.00318

AC:

AN:

3478

EpiCase

AF:

0.00185

EpiControl

AF:

0.00213

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 19, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.48

CADD

Benign

0.13

DANN

Benign

0.49

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over