13-30657376-C-T

Position:

• chr13-30657376-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.1397-98C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.419 in 1,208,444 control chromosomes in the GnomAD database, including 113,415 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 0.50 (21520 hom., cov: 32)
  • Exomes 𝑓: 0.41 (91895 hom.)
• Consequence: USPL1 NM_005800.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.167

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 (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.768 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
USPL1	NM_005800.5	c.1397-98C>T		intron_variant		ENST00000255304.9	NP_005791.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
USPL1	ENST00000255304.9	c.1397-98C>T		intron_variant		1	NM_005800.5	ENSP00000255304	P1
USPL1	ENST00000614860.1	c.410-98C>T		intron_variant		1		ENSP00000480656

Frequencies

GnomAD3 genomes AF: 0.499 AC: 75781 AN: 151884 Hom.: 21472 Cov.: 32

Gnomad AFR AF: 0.775

Gnomad AMI AF: 0.410

Gnomad AMR AF: 0.439

Gnomad ASJ AF: 0.418

Gnomad EAS AF: 0.164

Gnomad SAS AF: 0.467

Gnomad FIN AF: 0.303

Gnomad MID AF: 0.642

Gnomad NFE AF: 0.407

Gnomad OTH AF: 0.497

GnomAD4 exome AF: 0.407 AC: 430404 AN: 1056442 Hom.: 91895 AF XY: 0.410 AC XY: 214715 AN XY: 524120

Gnomad4 AFR exome AF: 0.791

Gnomad4 AMR exome AF: 0.387

Gnomad4 ASJ exome AF: 0.422

Gnomad4 EAS exome AF: 0.169

Gnomad4 SAS exome AF: 0.481

Gnomad4 FIN exome AF: 0.303

Gnomad4 NFE exome AF: 0.405

Gnomad4 OTH exome AF: 0.432

GnomAD4 genome AF: 0.499 AC: 75875 AN: 152002 Hom.: 21520 Cov.: 32 AF XY: 0.491 AC XY: 36477 AN XY: 74284

Gnomad4 AFR AF: 0.775

Gnomad4 AMR AF: 0.438

Gnomad4 ASJ AF: 0.418

Gnomad4 EAS AF: 0.164

Gnomad4 SAS AF: 0.467

Gnomad4 FIN AF: 0.303

Gnomad4 NFE AF: 0.407

Gnomad4 OTH AF: 0.494

Alfa AF: 0.466 Hom.: 2883

Bravo AF: 0.521

Asia WGS AF: 0.368 AC: 1279 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.8
DANN	Benign	0.71

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: rs7983138; hg19: chr13-31231513; COSMIC: COSV55000229;