rs2279308

Variant names:

• chr17-78798899-A-G
• rs2279308
• NM_001385174.1:c.3240+9T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 23 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.597 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.3240+9T>C		intron	N/A	NP_001372103.1	Q9P275
	USP36	NM_001385169.1		c.3243+9T>C		intron	N/A	NP_001372098.1
	USP36	NM_001321291.2		c.3240+9T>C		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.3240+9T>C		intron	N/A	ENSP00000401119.4	Q9P275
	USP36	ENST00000542802.7	TSL:1	c.3240+9T>C		intron	N/A	ENSP00000441214.1	Q9P275
	USP36	ENST00000589225.5	TSL:1	n.3240+9T>C		intron	N/A	ENSP00000467280.1	Q9P275

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

GnomAD2 exomes AF: 0.558 AC: 140253 AN: 251172 AF XY: 0.559

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 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

African (AFR) AF: 0.489 AC: 16375 AN: 33474

American (AMR) AF: 0.473 AC: 21140 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.561 AC: 14667 AN: 26132

East Asian (EAS) AF: 0.613 AC: 24353 AN: 39700

South Asian (SAS) AF: 0.525 AC: 45278 AN: 86248

European-Finnish (FIN) AF: 0.636 AC: 33879 AN: 53230

Middle Eastern (MID) AF: 0.485 AC: 2796 AN: 5766

European-Non Finnish (NFE) AF: 0.581 AC: 646099 AN: 1111680

Other (OTH) AF: 0.563 AC: 34012 AN: 60376

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

African (AFR) AF: 0.488 AC: 20237 AN: 41438

American (AMR) AF: 0.505 AC: 7708 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.551 AC: 1907 AN: 3464

East Asian (EAS) AF: 0.615 AC: 3165 AN: 5144

South Asian (SAS) AF: 0.548 AC: 2638 AN: 4812

European-Finnish (FIN) AF: 0.634 AC: 6694 AN: 10554

Middle Eastern (MID) AF: 0.507 AC: 149 AN: 294

European-Non Finnish (NFE) AF: 0.585 AC: 39769 AN: 67966

Other (OTH) AF: 0.546 AC: 1152 AN: 2110

Alfa AF: 0.566 Hom.: 18256

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.045
DANN	Benign	0.19
PhyloP100		-1.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs2279308; hg19: chr17-76794981; COSMIC: COSV61750841; COSMIC: COSV61750841;