Variant chr13-30646969-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

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

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 made for transcript

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
USPL1	NM_005800.5 linkuse as main transcript	c.1150C>T	p.Pro384Ser	missense_variant	7/9	ENST00000255304.9	NP_005791.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
USPL1	ENST00000255304.9 linkuse as main transcript	c.1150C>T	p.Pro384Ser	missense_variant	7/9	1	NM_005800.5	ENSP00000255304	P1	Q5W0Q7-1
USPL1	ENST00000614860.1 linkuse as main transcript	c.163C>T	p.Pro55Ser	missense_variant	5/7	1		ENSP00000480656		Q5W0Q7-2

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

GnomAD3 exomes

AF:

0.0384

AC:

9654

AN:

251166

Hom.:

283

AF XY:

0.0426

AC XY:

5780

AN XY:

135752

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 SAS exome

AF:

0.0960

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

Gnomad4 AFR exome

AF:

0.00502

Gnomad4 AMR exome

AF:

0.0131

Gnomad4 ASJ exome

AF:

0.0439

Gnomad4 EAS exome

AF:

0.0581

Gnomad4 SAS exome

AF:

0.0943

Gnomad4 FIN exome

AF:

0.0262

Gnomad4 NFE exome

AF:

0.0362

Gnomad4 OTH exome

AF:

0.0412

GnomAD4 genome

AF:

0.0263

AC:

4008

AN:

152128

Hom.:

Cov.:

AF XY:

0.0268

AC XY:

1993

AN XY:

74368

show subpopulations

Gnomad4 AFR

AF:

0.00663

Gnomad4 AMR

AF:

0.0175

Gnomad4 ASJ

AF:

0.0343

Gnomad4 EAS

AF:

0.0488

Gnomad4 SAS

AF:

0.0878

Gnomad4 FIN

AF:

0.0216

Gnomad4 NFE

AF:

0.0344

Gnomad4 OTH

AF:

0.0341

Alfa

AF:

0.0350

Hom.:

253

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

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;.

MutationTaster

Benign

0.99

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

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over