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GeneBe

6-83523633-C-A

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

2

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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.48).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
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
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-0.679 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
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
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 11 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PRSS35NM_153362.3 linkuse as main transcriptc.192C>A p.Ile64= synonymous_variant 2/2 ENST00000369700.4
PRSS35NM_001170423.2 linkuse as main transcriptc.192C>A p.Ile64= synonymous_variant 3/3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PRSS35ENST00000369700.4 linkuse as main transcriptc.192C>A p.Ile64= synonymous_variant 2/21 NM_153362.3 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00557
AC:
848
AN:
152114
Hom.:
11
Cov.:
32
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.:
3
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.:
16
Cov.:
31
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
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00562
AC:
856
AN:
152232
Hom.:
11
Cov.:
32
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.:
2
Bravo
AF:
0.00635
Asia WGS
AF:
0.00318
AC:
11
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 submitterclinical testingInvitaeFeb 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.

Other links and lift over

dbSNP: rs34790062; hg19: chr6-84233352; API