rs3088040

Positions:

• chr17-78803778-T-C
• chr17-78803778-T-G

Variant summary

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

The NM_001385174.1(USP36):​c.2417A>G​(p.Gln806Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.555 in 1,612,380 control chromosomes in the GnomAD database, including 249,854 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.57 (24597 hom., cov: 32)
  • Exomes 𝑓: 0.55 (225257 hom.)
• Consequence: USP36 NM_001385174.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.80

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 (MetaRNN=4.7939056E-6).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.593 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
USP36	NM_001385174.1	c.2417A>G	p.Gln806Arg	missense_variant	16/21	ENST00000449938.7	NP_001372103.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
USP36	ENST00000449938.7	c.2417A>G	p.Gln806Arg	missense_variant	16/21	1	NM_001385174.1	ENSP00000401119.4

Frequencies

GnomAD3 genomes AF: 0.568 AC: 86337 AN: 151920 Hom.: 24567 Cov.: 32

Gnomad AFR AF: 0.594

Gnomad AMI AF: 0.418

Gnomad AMR AF: 0.502

Gnomad ASJ AF: 0.543

Gnomad EAS AF: 0.612

Gnomad SAS AF: 0.534

Gnomad FIN AF: 0.626

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.562

Gnomad OTH AF: 0.552

GnomAD3 exomes AF: 0.549 AC: 135362 AN: 246648 Hom.: 37511 AF XY: 0.546 AC XY: 73474 AN XY: 134590

Gnomad AFR exome AF: 0.601

Gnomad AMR exome AF: 0.469

Gnomad ASJ exome AF: 0.553

Gnomad EAS exome AF: 0.604

Gnomad SAS exome AF: 0.506

Gnomad FIN exome AF: 0.636

Gnomad NFE exome AF: 0.553

Gnomad OTH exome AF: 0.535

GnomAD4 exome AF: 0.554 AC: 808789 AN: 1460342 Hom.: 225257 Cov.: 74 AF XY: 0.552 AC XY: 401053 AN XY: 726472

Gnomad4 AFR exome AF: 0.598

Gnomad4 AMR exome AF: 0.469

Gnomad4 ASJ exome AF: 0.556

Gnomad4 EAS exome AF: 0.612

Gnomad4 SAS exome AF: 0.504

Gnomad4 FIN exome AF: 0.626

Gnomad4 NFE exome AF: 0.555

Gnomad4 OTH exome AF: 0.549

GnomAD4 genome AF: 0.568 AC: 86433 AN: 152038 Hom.: 24597 Cov.: 32 AF XY: 0.571 AC XY: 42422 AN XY: 74310

Gnomad4 AFR AF: 0.594

Gnomad4 AMR AF: 0.503

Gnomad4 ASJ AF: 0.543

Gnomad4 EAS AF: 0.611

Gnomad4 SAS AF: 0.534

Gnomad4 FIN AF: 0.626

Gnomad4 NFE AF: 0.562

Gnomad4 OTH AF: 0.554

Alfa AF: 0.548 Hom.: 43308

Bravo AF: 0.552

TwinsUK AF: 0.556 AC: 2061

ALSPAC AF: 0.561 AC: 2161

ESP6500AA AF: 0.572 AC: 2477

ESP6500EA AF: 0.545 AC: 4634

ExAC AF: 0.545 AC: 65732

Asia WGS AF: 0.606 AC: 2107 AN: 3476

EpiCase AF: 0.546

EpiControl AF: 0.550

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.062
BayesDel_addAF	Benign	-0.88	T
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.019
DANN	Benign	0.13
DEOGEN2	Benign	0.0086	T;T
Eigen	Benign	-2.0
Eigen_PC	Benign	-2.1
FATHMM_MKL	Benign	0.022	N
LIST_S2	Benign	0.14	.;T
MetaRNN	Benign	0.0000048	T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.95	L;L
PrimateAI	Benign	0.17	T
PROVEAN	Benign	-0.71	N;N
REVEL	Benign	0.0030
Sift	Benign	0.95	T;T
Sift4G	Benign	0.69	T;T
Polyphen		0.0	B;B
Vest4		0.018
MPC		0.075
ClinPred		0.0096	T
GERP RS		-8.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.033
gMVP		0.10

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs3088040; hg19: chr17-76799860; COSMIC: COSV61753149; COSMIC: COSV61753149;