17-78826086-T-C

Position:

• chr17-78826086-T-C

Variant summary

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

The NM_001385174.1(USP36):​c.689+1159A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.399 in 152,028 control chromosomes in the GnomAD database, including 14,530 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 0.40 (14530 hom., cov: 31)
• Consequence: USP36 NM_001385174.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.04

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]

USP36 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.53 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
USP36	NM_001385174.1	c.689+1159A>G		intron_variant		ENST00000449938.7	NP_001372103.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
USP36	ENST00000449938.7	c.689+1159A>G		intron_variant		1	NM_001385174.1	ENSP00000401119.4

Frequencies

GnomAD3 genomes AF: 0.400 AC: 60715 AN: 151910 Hom.: 14528 Cov.: 31

Gnomad AFR AF: 0.123

Gnomad AMI AF: 0.403

Gnomad AMR AF: 0.417

Gnomad ASJ AF: 0.491

Gnomad EAS AF: 0.406

Gnomad SAS AF: 0.370

Gnomad FIN AF: 0.573

Gnomad MID AF: 0.385

Gnomad NFE AF: 0.534

Gnomad OTH AF: 0.415

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

GnomAD4 genome AF: 0.399 AC: 60719 AN: 152028 Hom.: 14530 Cov.: 31 AF XY: 0.401 AC XY: 29786 AN XY: 74286

Gnomad4 AFR AF: 0.122

Gnomad4 AMR AF: 0.417

Gnomad4 ASJ AF: 0.491

Gnomad4 EAS AF: 0.405

Gnomad4 SAS AF: 0.369

Gnomad4 FIN AF: 0.573

Gnomad4 NFE AF: 0.534

Gnomad4 OTH AF: 0.415

Alfa AF: 0.459 Hom.: 2814

Bravo AF: 0.371

Asia WGS AF: 0.404 AC: 1400 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.2
DANN	Benign	0.67

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: rs1531797; hg19: chr17-76822168;