Genetic Variant NM_001391956.1:c.4880G>A (chr10-73498804-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001391956.1(USP54):c.4880G>A(p.Arg1627Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000171 in 1,582,904 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000017 ( 0 hom. )

Consequence

USP54
NM_001391956.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.48

Publications

1 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:

PPP3CB-AS1 (HGNC:50750): (PPP3CB antisense RNA 1 (head to head))

PPP3CB-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06854451).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001391956.1. 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.4880G>A	p.Arg1627Gln	missense	Exon 24 of 24	NP_001378885.1	Q70EL1-1
USP54	NM_001391941.1		c.4946G>A	p.Arg1649Gln	missense	Exon 24 of 24	NP_001378870.1
USP54	NM_001391953.1		c.4880G>A	p.Arg1627Gln	missense	Exon 24 of 24	NP_001378882.1	Q70EL1-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
USP54	ENST00000687698.1	MANE Select	c.4880G>A	p.Arg1627Gln	missense	Exon 24 of 24	ENSP00000510226.1	Q70EL1-1
USP54	ENST00000422491.7	TSL:1	c.*1845G>A		3_prime_UTR	Exon 20 of 20	ENSP00000407368.4	A0A804D9U3
PPP3CB-AS1	ENST00000422977.3	TSL:1	n.1206-791C>T		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0000202

AC:

AN:

148690

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000245

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000298

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000200

AC:

AN:

250242

AF XY:

0.0000222

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000265

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000167

AC:

AN:

1434214

Hom.:

Cov.:

AF XY:

0.0000154

AC XY:

AN XY:

712986

show subpopulations

African (AFR)

AF:

0.0000305

AC:

AN:

32786

American (AMR)

AF:

0.00

AC:

AN:

43774

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25128

East Asian (EAS)

AF:

0.00

AC:

AN:

37792

South Asian (SAS)

AF:

0.0000116

AC:

AN:

85854

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50514

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5620

European-Non Finnish (NFE)

AF:

0.0000201

AC:

AN:

1094138

Other (OTH)

AF:

0.00

AC:

AN:

58608

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.0000202

AC:

AN:

148690

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

72564

show subpopulations

African (AFR)

AF:

0.0000245

AC:

AN:

40760

American (AMR)

AF:

0.00

AC:

AN:

14960

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3424

East Asian (EAS)

AF:

0.00

AC:

AN:

4846

South Asian (SAS)

AF:

0.00

AC:

AN:

4510

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9852

Middle Eastern (MID)

AF:

0.00

AC:

AN:

312

European-Non Finnish (NFE)

AF:

0.0000298

AC:

AN:

67082

Other (OTH)

AF:

0.00

AC:

AN:

2058

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.558

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00

Hom.:

Bravo

AF:

0.0000189

ExAC

AF:

0.0000247

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.49

CADD

Benign

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.0066

Eigen

Benign

-0.32

Eigen_PC

Benign

-0.27

FATHMM_MKL

Benign

0.045

LIST_S2

Benign

0.77

M_CAP

Benign

0.019

MetaRNN

Benign

0.069

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.0

PhyloP100

1.5

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.85

REVEL

Benign

0.057

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.060

Polyphen

0.026

Vest4

0.084

MutPred

0.12

Gain of relative solvent accessibility (P = 0.0166)

MVP

0.32

MPC

0.19

ClinPred

0.23

GERP RS

4.3

Varity_R

0.058

gMVP

0.17

Mutation Taster

=93/7

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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