17-78815721-C-T

Variant names:

• chr17-78815721-C-T
• rs7218605
• NM_001385174.1:c.1024-1169G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 10 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001385174.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USP36	NM_001385174.1	MANE Select	c.1024-1169G>A		intron	N/A	NP_001372103.1	Q9P275
	USP36	NM_001385169.1		c.1024-1169G>A		intron	N/A	NP_001372098.1
	USP36	NM_001321291.2		c.1024-1169G>A		intron	N/A	NP_001308220.1	Q9P275

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USP36	ENST00000449938.7	TSL:1 MANE Select	c.1024-1169G>A		intron	N/A	ENSP00000401119.4	Q9P275
	USP36	ENST00000542802.7	TSL:1	c.1024-1169G>A		intron	N/A	ENSP00000441214.1	Q9P275
	USP36	ENST00000588086.6	TSL:1	n.1024-1169G>A		intron	N/A	ENSP00000468549.3	A0A075B784

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

African (AFR) AF: 0.423 AC: 17534 AN: 41462

American (AMR) AF: 0.452 AC: 6886 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.515 AC: 1786 AN: 3468

East Asian (EAS) AF: 0.496 AC: 2557 AN: 5154

South Asian (SAS) AF: 0.373 AC: 1795 AN: 4812

European-Finnish (FIN) AF: 0.577 AC: 6071 AN: 10528

Middle Eastern (MID) AF: 0.425 AC: 125 AN: 294

European-Non Finnish (NFE) AF: 0.531 AC: 36052 AN: 67914

Other (OTH) AF: 0.489 AC: 1031 AN: 2110

Alfa AF: 0.506 Hom.: 8669

Bravo AF: 0.473

Asia WGS AF: 0.474 AC: 1646 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.20
DANN	Benign	0.61
PhyloP100		-2.4
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7218605; hg19: chr17-76811803;