rs3088040

Variant names:

• chr17-78803778-T-C
• rs3088040
• NM_001385174.1:c.2417A>G

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000449938.7(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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.57 (24597 hom., cov: 32)
  • Exomes 𝑓: 0.55 (225257 hom.)
• Consequence: USP36 ENST00000449938.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.80
• Publications: 38 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 (MetaRNN=4.7939056E-6).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.593 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000449938.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USP36	NM_001385174.1	MANE Select	c.2417A>G	p.Gln806Arg	missense	Exon 16 of 21	NP_001372103.1
	USP36	NM_001385169.1		c.2417A>G	p.Gln806Arg	missense	Exon 16 of 21	NP_001372098.1
	USP36	NM_001321291.2		c.2417A>G	p.Gln806Arg	missense	Exon 16 of 21	NP_001308220.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USP36	ENST00000449938.7	TSL:1 MANE Select	c.2417A>G	p.Gln806Arg	missense	Exon 16 of 21	ENSP00000401119.4
	USP36	ENST00000542802.7	TSL:1	c.2417A>G	p.Gln806Arg	missense	Exon 16 of 21	ENSP00000441214.1
	USP36	ENST00000588086.6	TSL:1	n.*125A>G		non_coding_transcript_exon	Exon 16 of 16	ENSP00000468549.3

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

GnomAD2 exomes AF: 0.549 AC: 135362 AN: 246648 AF XY: 0.546

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 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

African (AFR) AF: 0.598 AC: 20004 AN: 33474

American (AMR) AF: 0.469 AC: 20959 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.556 AC: 14540 AN: 26132

East Asian (EAS) AF: 0.612 AC: 24276 AN: 39696

South Asian (SAS) AF: 0.504 AC: 43453 AN: 86232

European-Finnish (FIN) AF: 0.626 AC: 32740 AN: 52262

Middle Eastern (MID) AF: 0.464 AC: 2587 AN: 5578

European-Non Finnish (NFE) AF: 0.555 AC: 617077 AN: 1111898

Other (OTH) AF: 0.549 AC: 33153 AN: 60352

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

African (AFR) AF: 0.594 AC: 24643 AN: 41456

American (AMR) AF: 0.503 AC: 7683 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.543 AC: 1886 AN: 3472

East Asian (EAS) AF: 0.611 AC: 3154 AN: 5164

South Asian (SAS) AF: 0.534 AC: 2573 AN: 4820

European-Finnish (FIN) AF: 0.626 AC: 6615 AN: 10566

Middle Eastern (MID) AF: 0.510 AC: 150 AN: 294

European-Non Finnish (NFE) AF: 0.562 AC: 38180 AN: 67960

Other (OTH) AF: 0.554 AC: 1169 AN: 2110

Alfa AF: 0.551 Hom.: 58785

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 v4.9

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
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
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.95	L
PhyloP100		-1.8
PrimateAI	Benign	0.17	T
PROVEAN	Benign	-0.71	N
REVEL	Benign	0.0030
Sift	Benign	0.95	T
Sift4G	Benign	0.69	T
Polyphen		0.0	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
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3088040; hg19: chr17-76799860; COSMIC: COSV61753149; COSMIC: COSV61753149;