rs3742303

chr13-30646969-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.04

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]

ACMG classification

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	UniProt
USPL1	NM_005800.5	c.1150C>T	p.Pro384Ser	missense_variant	7/9	ENST00000255304.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
USPL1	ENST00000255304.9	c.1150C>T	p.Pro384Ser	missense_variant	7/9	1	NM_005800.5	P1
USPL1	ENST00000614860.1	c.163C>T	p.Pro55Ser	missense_variant	5/7	1

Frequencies

GnomAD3 genomes AF: 0.0264 AC: 4010 AN: 152010 Hom.: 96 Cov.: 32

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

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.: 30 AF XY: 0.0406 AC XY: 29538 AN XY: 727070

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.: 96 Cov.: 32 AF XY: 0.0268 AC XY: 1993 AN XY: 74368

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: 30

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	T
BayesDel_noAF	Benign	-0.46
Cadd	Benign	20
Dann	Uncertain	1.0
DEOGEN2	Benign	0.12	T;.
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Benign	0.76	T;T
MetaRNN	Benign	0.0022	T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.9	L;.
MutationTaster	Benign	0.99	D
PrimateAI	Benign	0.45	T
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	T
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

Other links and lift over

dbSNP: rs3742303; hg19: chr13-31221106; COSMIC: COSV55001671;