dbSNP rs12255505: USP54:c.2060+79G>T (chr10-73529601-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001391956.1(USP54):c.2060+79G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.103 in 1,522,264 control chromosomes in the GnomAD database, including 15,384 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 0.19 ( 4971 hom., cov: 32)

Exomes 𝑓: 0.093 ( 10413 hom. )

Consequence

USP54
NM_001391956.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.716

Publications

9 publications found

Variant links:

Genes affected

USP54 (HGNC:23513): (ubiquitin specific peptidase 54) Predicted to enable thiol-dependent deubiquitinase. Predicted to be involved in protein deubiquitination. [provided by Alliance of Genome Resources, Apr 2022]

USP54 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=-0.89).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.442 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
USP54	NM_001391956.1 link	c.2060+79G>T		intron_variant	Intron 15 of 23	ENST00000687698.1	NP_001378885.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
USP54	ENST00000687698.1 link	c.2060+79G>T		intron_variant	Intron 15 of 23		NM_001391956.1	ENSP00000510226.1		Q70EL1-1

Frequencies

GnomAD3 genomes

AF:

0.188

AC:

28653

AN:

152016

Hom.:

4945

Cov.:

show subpopulations

Gnomad AFR

AF:

0.447

Gnomad AMI

AF:

0.108

Gnomad AMR

AF:

0.114

Gnomad ASJ

AF:

0.131

Gnomad EAS

AF:

0.297

Gnomad SAS

AF:

0.226

Gnomad FIN

AF:

0.0448

Gnomad MID

AF:

0.0981

Gnomad NFE

AF:

0.0654

Gnomad OTH

AF:

0.145

GnomAD2 exomes

AF:

0.134

AC:

32832

AN:

245476

AF XY:

0.132

show subpopulations

Gnomad AFR exome

AF:

0.457

Gnomad AMR exome

AF:

0.0984

Gnomad ASJ exome

AF:

0.133

Gnomad EAS exome

AF:

0.301

Gnomad FIN exome

AF:

0.0477

Gnomad NFE exome

AF:

0.0659

Gnomad OTH exome

AF:

0.0953

GnomAD4 exome

AF:

0.0932

AC:

127761

AN:

1370130

Hom.:

10413

Cov.:

AF XY:

0.0960

AC XY:

65904

AN XY:

686294

show subpopulations

African (AFR)

AF:

0.458

AC:

14394

AN:

31462

American (AMR)

AF:

0.0998

AC:

4450

AN:

44592

Ashkenazi Jewish (ASJ)

AF:

0.127

AC:

3264

AN:

25608

East Asian (EAS)

AF:

0.285

AC:

11168

AN:

39250

South Asian (SAS)

AF:

0.220

AC:

18465

AN:

83910

European-Finnish (FIN)

AF:

0.0489

AC:

2547

AN:

52074

Middle Eastern (MID)

AF:

0.0896

AC:

502

AN:

5600

European-Non Finnish (NFE)

AF:

0.0644

AC:

66329

AN:

1030272

Other (OTH)

AF:

0.116

AC:

6642

AN:

57362

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

5624

11248

16872

22496

28120

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2838

5676

8514

11352

14190

<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:

0.189

AC:

28734

AN:

152134

Hom.:

4971

Cov.:

AF XY:

0.189

AC XY:

14044

AN XY:

74406

show subpopulations

African (AFR)

AF:

0.447

AC:

18548

AN:

41450

American (AMR)

AF:

0.114

AC:

1744

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.131

AC:

454

AN:

3470

East Asian (EAS)

AF:

0.298

AC:

1542

AN:

5180

South Asian (SAS)

AF:

0.224

AC:

1081

AN:

4818

European-Finnish (FIN)

AF:

0.0448

AC:

476

AN:

10616

Middle Eastern (MID)

AF:

0.102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0654

AC:

4450

AN:

67996

Other (OTH)

AF:

0.147

AC:

311

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

962

1924

2886

3848

4810

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

278

556

834

1112

1390

<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:

0.124

Hom.:

3442

Bravo

AF:

0.203

Asia WGS

AF:

0.269

AC:

935

AN:

3478

EpiCase

AF:

0.0650

EpiControl

AF:

0.0644

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.77

(source)

DANN

Benign

0.40

PhyloP100

-0.72

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