Genetic Variant USP53:c.973-864C>T (chr4-119266456-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001371395.1(USP53):c.973-864C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.279 in 408,598 control chromosomes in the GnomAD database, including 16,668 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 0.28 ( 6195 hom., cov: 32)

Exomes 𝑓: 0.28 ( 10473 hom. )

Consequence

USP53
NM_001371395.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.143

Publications

19 publications found

Variant links:

Genes affected

USP53 (HGNC:29255): (ubiquitin specific peptidase 53) Predicted to enable thiol-dependent deubiquitinase. Predicted to be involved in response to auditory stimulus and sensory perception of sound. Predicted to act upstream of or within action potential and neuron apoptotic process. Predicted to be located in bicellular tight junction. Predicted to be active in cell-cell junction. [provided by Alliance of Genome Resources, Apr 2022]

USP53 Gene-Disease associations (from GenCC):

cholestasis
Inheritance: AR Classification: STRONG Submitted by: Ambry Genetics
cholestasis, progressive familial intrahepatic, 7, with or without hearing loss
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

USP53 links:

Genome browser will be placed here

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=-0.92).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.37 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
USP53	NM_001371395.1 link	c.973-864C>T		intron_variant	Intron 12 of 18	ENST00000692078.1	NP_001358324.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
USP53	ENST00000692078.1 link	c.973-864C>T		intron_variant	Intron 12 of 18		NM_001371395.1	ENSP00000509606.1		Q70EK8

Frequencies

GnomAD3 genomes

AF:

0.281

AC:

42650

AN:

151794

Hom.:

6193

Cov.:

show subpopulations

Gnomad AFR

AF:

0.220

Gnomad AMI

AF:

0.325

Gnomad AMR

AF:

0.275

Gnomad ASJ

AF:

0.211

Gnomad EAS

AF:

0.384

Gnomad SAS

AF:

0.187

Gnomad FIN

AF:

0.266

Gnomad MID

AF:

0.236

Gnomad NFE

AF:

0.323

Gnomad OTH

AF:

0.297

GnomAD4 exome

AF:

0.278

AC:

71262

AN:

256684

Hom.:

10473

AF XY:

0.266

AC XY:

38816

AN XY:

145720

show subpopulations

African (AFR)

AF:

0.222

AC:

1506

AN:

6790

American (AMR)

AF:

0.290

AC:

5696

AN:

19668

Ashkenazi Jewish (ASJ)

AF:

0.213

AC:

1692

AN:

7940

East Asian (EAS)

AF:

0.382

AC:

3292

AN:

8622

South Asian (SAS)

AF:

0.172

AC:

8703

AN:

50658

European-Finnish (FIN)

AF:

0.268

AC:

2896

AN:

10826

Middle Eastern (MID)

AF:

0.205

AC:

331

AN:

1618

European-Non Finnish (NFE)

AF:

0.316

AC:

43775

AN:

138396

Other (OTH)

AF:

0.277

AC:

3371

AN:

12166

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

2363

4725

7088

9450

11813

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

262

524

786

1048

1310

<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:

0.281

AC:

42666

AN:

151914

Hom.:

6195

Cov.:

AF XY:

0.278

AC XY:

20603

AN XY:

74226

show subpopulations

African (AFR)

AF:

0.220

AC:

9118

AN:

41432

American (AMR)

AF:

0.275

AC:

4194

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.211

AC:

730

AN:

3462

East Asian (EAS)

AF:

0.384

AC:

1983

AN:

5160

South Asian (SAS)

AF:

0.186

AC:

898

AN:

4824

European-Finnish (FIN)

AF:

0.266

AC:

2807

AN:

10534

Middle Eastern (MID)

AF:

0.236

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.323

AC:

21950

AN:

67932

Other (OTH)

AF:

0.295

AC:

621

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1560

3121

4681

6242

7802

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

438

876

1314

1752

2190

<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:

0.304

Hom.:

17539

Bravo

AF:

0.286

Asia WGS

AF:

0.259

AC:

902

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

3.5

(source)

DANN

Benign

0.57

PhyloP100

-0.14

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over