17-78803684-A-G

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_001385174.1(USP36):c.2511T>C(p.Thr837=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00163 in 1,610,252 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0012 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0017 (3 hom.)
• Consequence: USP36 NM_001385174.1 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.61

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]

ACMG classification

Verdict is Benign. Variant got -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 17-78803684-A-G is Benign according to our data. Variant chr17-78803684-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2648380.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.61 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
USP36	NM_001385174.1	c.2511T>C	p.Thr837=	synonymous_variant	16/21	ENST00000449938.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
USP36	ENST00000449938.7	c.2511T>C	p.Thr837=	synonymous_variant	16/21	1	NM_001385174.1	P1

Frequencies

GnomAD3 genomes AF: 0.00116 AC: 177 AN: 151946 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000314

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00111

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000209

Gnomad FIN AF: 0.000472

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00206

Gnomad OTH AF: 0.000479

GnomAD3 exomes AF: 0.00128 AC: 315 AN: 245948 Hom.: 0 AF XY: 0.00133 AC XY: 179 AN XY: 134084

Gnomad AFR exome AF: 0.000200

Gnomad AMR exome AF: 0.000204

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000328

Gnomad FIN exome AF: 0.000576

Gnomad NFE exome AF: 0.00252

Gnomad OTH exome AF: 0.000498

GnomAD4 exome AF: 0.00168 AC: 2445 AN: 1458306 Hom.: 3 Cov.: 31 AF XY: 0.00162 AC XY: 1173 AN XY: 725418

Gnomad4 AFR exome AF: 0.000150

Gnomad4 AMR exome AF: 0.000337

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000244

Gnomad4 FIN exome AF: 0.000465

Gnomad4 NFE exome AF: 0.00208

Gnomad4 OTH exome AF: 0.00111

GnomAD4 genome AF: 0.00116 AC: 177 AN: 151946 Hom.: 0 Cov.: 32 AF XY: 0.00112 AC XY: 83 AN XY: 74206

Gnomad4 AFR AF: 0.000314

Gnomad4 AMR AF: 0.00111

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000209

Gnomad4 FIN AF: 0.000472

Gnomad4 NFE AF: 0.00206

Gnomad4 OTH AF: 0.000479

Alfa AF: 0.00181 Hom.: 0

Bravo AF: 0.00102

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00109

EpiControl AF: 0.00213

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Apr 01, 2022

USP36: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.096
Dann	Benign	0.32

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: rs145591044; hg19: chr17-76799766;