rs2279308

Positions:

• chr17-78798899-A-G

Variant summary

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

The NM_001385174.1(USP36):​c.3240+9T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.572 in 1,613,272 control chromosomes in the GnomAD database, including 265,255 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 0.55 (23243 hom., cov: 31)
  • Exomes 𝑓: 0.57 (242012 hom.)
• Consequence: USP36 NM_001385174.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.28

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.597 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
USP36	NM_001385174.1	c.3240+9T>C		intron_variant		ENST00000449938.7	NP_001372103.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
USP36	ENST00000449938.7	c.3240+9T>C		intron_variant		1	NM_001385174.1	ENSP00000401119	P1

Frequencies

GnomAD3 genomes AF: 0.552 AC: 83775 AN: 151832 Hom.: 23234 Cov.: 31

Gnomad AFR AF: 0.489

Gnomad AMI AF: 0.449

Gnomad AMR AF: 0.505

Gnomad ASJ AF: 0.551

Gnomad EAS AF: 0.616

Gnomad SAS AF: 0.549

Gnomad FIN AF: 0.634

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.585

Gnomad OTH AF: 0.543

GnomAD3 exomes AF: 0.558 AC: 140253 AN: 251172 Hom.: 39578 AF XY: 0.559 AC XY: 75919 AN XY: 135762

Gnomad AFR exome AF: 0.486

Gnomad AMR exome AF: 0.473

Gnomad ASJ exome AF: 0.562

Gnomad EAS exome AF: 0.605

Gnomad SAS exome AF: 0.526

Gnomad FIN exome AF: 0.647

Gnomad NFE exome AF: 0.579

Gnomad OTH exome AF: 0.553

GnomAD4 exome AF: 0.574 AC: 838599 AN: 1461322 Hom.: 242012 Cov.: 41 AF XY: 0.573 AC XY: 416289 AN XY: 726996

Gnomad4 AFR exome AF: 0.489

Gnomad4 AMR exome AF: 0.473

Gnomad4 ASJ exome AF: 0.561

Gnomad4 EAS exome AF: 0.613

Gnomad4 SAS exome AF: 0.525

Gnomad4 FIN exome AF: 0.636

Gnomad4 NFE exome AF: 0.581

Gnomad4 OTH exome AF: 0.563

GnomAD4 genome AF: 0.552 AC: 83827 AN: 151950 Hom.: 23243 Cov.: 31 AF XY: 0.555 AC XY: 41189 AN XY: 74246

Gnomad4 AFR AF: 0.488

Gnomad4 AMR AF: 0.505

Gnomad4 ASJ AF: 0.551

Gnomad4 EAS AF: 0.615

Gnomad4 SAS AF: 0.548

Gnomad4 FIN AF: 0.634

Gnomad4 NFE AF: 0.585

Gnomad4 OTH AF: 0.546

Alfa AF: 0.566 Hom.: 16875

Bravo AF: 0.531

Asia WGS AF: 0.607 AC: 2111 AN: 3478

EpiCase AF: 0.575

EpiControl AF: 0.577

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.045
DANN	Benign	0.19
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs2279308; hg19: chr17-76794981; COSMIC: COSV61750841; COSMIC: COSV61750841;