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GeneBe

17-78798504-G-A

Variant summary

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

The NM_001385174.1(USP36):c.3288C>T(p.Asn1096=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00205 in 1,614,022 control chromosomes in the GnomAD database, including 59 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.011 ( 29 hom., cov: 32)
Exomes 𝑓: 0.0011 ( 30 hom. )

Consequence

USP36
NM_001385174.1 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.443
Variant links:
Genes affected
USP36 (HGNC:20062): (ubiquitin specific peptidase 36) This gene encodes a member of the peptidase C19 or ubiquitin-specific protease family of cysteine proteases. Members of this family remove ubiquitin molecules from polyubiquitinated proteins. The encoded protein may deubiquitinate and stabilize the transcription factor c-Myc, also known as MYC, an important oncoprotein known to be upregulated in most human cancers. The encoded protease may also regulate the activation of autophagy. This gene exhibits elevated expression in some breast and lung cancers. [provided by RefSeq, Mar 2016]

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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=-0.65).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 17-78798504-G-A is Benign according to our data. Variant chr17-78798504-G-A is described in ClinVar as [Benign]. Clinvar id is 768918.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=-0.443 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 = 0.0109 (1657/152264) while in subpopulation AFR AF= 0.0384 (1595/41544). AF 95% confidence interval is 0.0368. There are 29 homozygotes in gnomad4. There are 725 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 30 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
USP36NM_001385174.1 linkuse as main transcriptc.3288C>T p.Asn1096= synonymous_variant 20/21 ENST00000449938.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
USP36ENST00000449938.7 linkuse as main transcriptc.3288C>T p.Asn1096= synonymous_variant 20/211 NM_001385174.1 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0109
AC:
1658
AN:
152144
Hom.:
30
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0385
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00223
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000147
Gnomad OTH
AF:
0.00813
GnomAD3 exomes
AF:
0.00298
AC:
750
AN:
251464
Hom.:
7
AF XY:
0.00194
AC XY:
263
AN XY:
135914
show subpopulations
Gnomad AFR exome
AF:
0.0409
Gnomad AMR exome
AF:
0.00156
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000193
Gnomad OTH exome
AF:
0.00130
GnomAD4 exome
AF:
0.00113
AC:
1655
AN:
1461758
Hom.:
30
Cov.:
31
AF XY:
0.000957
AC XY:
696
AN XY:
727204
show subpopulations
Gnomad4 AFR exome
AF:
0.0381
Gnomad4 AMR exome
AF:
0.00177
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000696
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000148
Gnomad4 OTH exome
AF:
0.00209
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0109
AC:
1657
AN:
152264
Hom.:
29
Cov.:
32
AF XY:
0.00974
AC XY:
725
AN XY:
74448
show subpopulations
Gnomad4 AFR
AF:
0.0384
Gnomad4 AMR
AF:
0.00222
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000147
Gnomad4 OTH
AF:
0.00804
Alfa
AF:
0.00579
Hom.:
9
Bravo
AF:
0.0118
Asia WGS
AF:
0.00346
AC:
13
AN:
3478
EpiCase
AF:
0.000382
EpiControl
AF:
0.000237

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 testingInvitaeMay 09, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.65
Cadd
Benign
8.0
Dann
Benign
0.71

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.12
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: rs73394916; hg19: chr17-76794586; API