Genetic Variant USPL1:p.Pro384Ser (chr13-30646969-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_005800.5(USPL1):c.1150C>T(p.Pro384Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0377 in 1,613,702 control chromosomes in the GnomAD database, including 1,525 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.026 ( 96 hom., cov: 32)

Exomes 𝑓: 0.039 ( 1429 hom. )

Consequence

USPL1
NM_005800.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.04

Publications

15 publications found

Variant links:

Genes affected

USPL1 (HGNC:20294): (ubiquitin specific peptidase like 1) Enables SUMO binding activity and SUMO-specific isopeptidase activity. Involved in several processes, including Cajal body organization; protein desumoylation; and snRNA transcription. Located in Cajal body. [provided by Alliance of Genome Resources, Apr 2022]

USPL1 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 (MetaRNN=0.0022166967).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0809 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
USPL1	NM_005800.5 link	c.1150C>T	p.Pro384Ser	missense_variant	Exon 7 of 9	ENST00000255304.9	NP_005791.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
USPL1	ENST00000255304.9 link	c.1150C>T	p.Pro384Ser	missense_variant	Exon 7 of 9	1	NM_005800.5	ENSP00000255304.4
USPL1	ENST00000614860.1 link	c.163C>T	p.Pro55Ser	missense_variant	Exon 5 of 7	1		ENSP00000480656.1

Frequencies

GnomAD3 genomes

AF:

0.0264

AC:

4010

AN:

152010

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00665

Gnomad AMI

AF:

0.0154

Gnomad AMR

AF:

0.0176

Gnomad ASJ

AF:

0.0343

Gnomad EAS

AF:

0.0487

Gnomad SAS

AF:

0.0880

Gnomad FIN

AF:

0.0216

Gnomad MID

AF:

0.0538

Gnomad NFE

AF:

0.0344

Gnomad OTH

AF:

0.0344

GnomAD2 exomes

AF:

0.0384

AC:

9654

AN:

251166

AF XY:

0.0426

show subpopulations

Gnomad AFR exome

AF:

0.00609

Gnomad AMR exome

AF:

0.0115

Gnomad ASJ exome

AF:

0.0426

Gnomad EAS exome

AF:

0.0479

Gnomad FIN exome

AF:

0.0242

Gnomad NFE exome

AF:

0.0367

Gnomad OTH exome

AF:

0.0353

GnomAD4 exome

AF:

0.0388

AC:

56768

AN:

1461574

Hom.:

1429

Cov.:

AF XY:

0.0406

AC XY:

29538

AN XY:

727070

show subpopulations

African (AFR)

AF:

0.00502

AC:

168

AN:

33466

American (AMR)

AF:

0.0131

AC:

588

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.0439

AC:

1147

AN:

26132

East Asian (EAS)

AF:

0.0581

AC:

2307

AN:

39674

South Asian (SAS)

AF:

0.0943

AC:

8127

AN:

86212

European-Finnish (FIN)

AF:

0.0262

AC:

1398

AN:

53408

Middle Eastern (MID)

AF:

0.0573

AC:

330

AN:

5764

European-Non Finnish (NFE)

AF:

0.0362

AC:

40213

AN:

1111834

Other (OTH)

AF:

0.0412

AC:

2490

AN:

60368

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

2528

5057

7585

10114

12642

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1604

3208

4812

6416

8020

<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:

0.0263

AC:

4008

AN:

152128

Hom.:

Cov.:

AF XY:

0.0268

AC XY:

1993

AN XY:

74368

show subpopulations

African (AFR)

AF:

0.00663

AC:

275

AN:

41482

American (AMR)

AF:

0.0175

AC:

268

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.0343

AC:

119

AN:

3470

East Asian (EAS)

AF:

0.0488

AC:

253

AN:

5182

South Asian (SAS)

AF:

0.0878

AC:

423

AN:

4816

European-Finnish (FIN)

AF:

0.0216

AC:

229

AN:

10578

Middle Eastern (MID)

AF:

0.0612

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0344

AC:

2337

AN:

67996

Other (OTH)

AF:

0.0341

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

194

388

582

776

970

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

116

174

232

290

<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:

0.0336

Hom.:

461

Bravo

AF:

0.0241

TwinsUK

AF:

0.0361

AC:

134

ALSPAC

AF:

0.0392

AC:

151

ESP6500AA

AF:

0.00681

AC:

ESP6500EA

AF:

0.0333

AC:

286

ExAC

AF:

0.0398

AC:

4827

Asia WGS

AF:

0.0490

AC:

170

AN:

3478

EpiCase

AF:

0.0382

EpiControl

AF:

0.0372

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.46

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.12

T;.

Eigen

Uncertain

0.49

Eigen_PC

Uncertain

0.48

FATHMM_MKL

Uncertain

0.80

LIST_S2

Benign

0.76

T;T

MetaRNN

Benign

0.0022

T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.9

L;.

PhyloP100

1.0

PrimateAI

Benign

0.45

PROVEAN

Pathogenic

-5.9

D;.

REVEL

Benign

0.20

Sift

Uncertain

0.0050

D;.

Sift4G

Pathogenic

0.0

D;D

Polyphen

0.99

D;.

Vest4

0.15

MPC

0.14

ClinPred

0.035

GERP RS

4.7

Varity_R

0.43

gMVP

0.54

Mutation Taster

=95/5

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