dbSNP rs2279308: USP36:c.3240+9T>C (chr17-78798899-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.28

Publications

23 publications found

Variant links:

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 links:

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new If you want to explore the variant's impact on the transcript NM_001385174.1, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

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

Gene	Transcript	Tags	HGVSc	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

Gene	Transcript	Tags	HGVSc	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.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.573

AC XY:

416289

AN XY:

726996

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

20584

41168

61752

82336

102920

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17730

35460

53190

70920

88650

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.552

AC:

83827

AN:

151950

Hom.:

23243

Cov.:

AF XY:

0.555

AC XY:

41189

AN XY:

74246

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1945

3890

5834

7779

9724

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

724

1448

2172

2896

3620

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

(source)

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)

(source)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over