17-78815721-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001385174.1(USP36):c.1024-1169G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.488 in 151,900 control chromosomes in the GnomAD database, including 18,293 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.49 (18293 hom., cov: 33)
• Consequence: USP36 NM_001385174.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.37

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.07).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.526 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
USP36	NM_001385174.1	c.1024-1169G>A		intron_variant		ENST00000449938.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
USP36	ENST00000449938.7	c.1024-1169G>A		intron_variant		1	NM_001385174.1	P1

Frequencies

GnomAD3 genomes AF: 0.488 AC: 74132 AN: 151782 Hom.: 18277 Cov.: 33

Gnomad AFR AF: 0.423

Gnomad AMI AF: 0.392

Gnomad AMR AF: 0.451

Gnomad ASJ AF: 0.515

Gnomad EAS AF: 0.497

Gnomad SAS AF: 0.373

Gnomad FIN AF: 0.577

Gnomad MID AF: 0.415

Gnomad NFE AF: 0.531

Gnomad OTH AF: 0.485

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.488 AC: 74194 AN: 151900 Hom.: 18293 Cov.: 33 AF XY: 0.489 AC XY: 36277 AN XY: 74190

Gnomad4 AFR AF: 0.423

Gnomad4 AMR AF: 0.452

Gnomad4 ASJ AF: 0.515

Gnomad4 EAS AF: 0.496

Gnomad4 SAS AF: 0.373

Gnomad4 FIN AF: 0.577

Gnomad4 NFE AF: 0.531

Gnomad4 OTH AF: 0.489

Alfa AF: 0.505 Hom.: 7568

Bravo AF: 0.473

Asia WGS AF: 0.474 AC: 1646 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
Cadd	Benign	0.20
Dann	Benign	0.61

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: rs7218605; hg19: chr17-76811803;