Genetic Variant USP54:c.2060+79G>T (chr10-73529601-C-A) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_001320441.2(USP54):c.2139G>T(p.Leu713Leu) variant causes a synonymous 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_001320441.2 synonymous

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 -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP7

Synonymous conserved (PhyloP=-0.716 with no splicing effect.

BA1

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001320441.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
USP54	NM_001391956.1	MANE Select	c.2060+79G>T		intron	N/A	NP_001378885.1	Q70EL1-1
USP54	NM_001320441.2		c.2139G>T	p.Leu713Leu	synonymous	Exon 15 of 15	NP_001307370.1
USP54	NM_001391941.1		c.2126+79G>T		intron	N/A	NP_001378870.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
USP54	ENST00000687698.1	MANE Select	c.2060+79G>T	intron	N/A	ENSP00000510226.1	Q70EL1-1
USP54	ENST00000422491.7	TSL:1	c.2060+79G>T	intron	N/A	ENSP00000407368.4	A0A804D9U3
USP54	ENST00000498143.5	TSL:1	n.2620+79G>T	intron	N/A

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 v4.9

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over