13-30657669-T-C

Position:

• chr13-30657669-T-C

Variant summary

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

The ENST00000255304.9(USPL1):​c.1592T>C​(p.Leu531Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.419 in 1,613,916 control chromosomes in the GnomAD database, including 149,975 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict 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 0.50 (21740 hom., cov: 32)
  • Exomes 𝑓: 0.41 (128235 hom.)
• Consequence: USPL1 ENST00000255304.9 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.508

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=1.2610923E-6).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.775 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
USPL1	NM_005800.5	c.1592T>C	p.Leu531Ser	missense_variant	9/9	ENST00000255304.9	NP_005791.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
USPL1	ENST00000255304.9	c.1592T>C	p.Leu531Ser	missense_variant	9/9	1	NM_005800.5	ENSP00000255304	P1
USPL1	ENST00000614860.1	c.605T>C	p.Leu202Ser	missense_variant	7/7	1		ENSP00000480656

Frequencies

GnomAD3 genomes AF: 0.501 AC: 76073 AN: 151956 Hom.: 21693 Cov.: 32

Gnomad AFR AF: 0.781

Gnomad AMI AF: 0.409

Gnomad AMR AF: 0.438

Gnomad ASJ AF: 0.418

Gnomad EAS AF: 0.164

Gnomad SAS AF: 0.467

Gnomad FIN AF: 0.301

Gnomad MID AF: 0.642

Gnomad NFE AF: 0.408

Gnomad OTH AF: 0.498

GnomAD3 exomes AF: 0.411 AC: 103217 AN: 251312 Hom.: 23431 AF XY: 0.414 AC XY: 56164 AN XY: 135818

Gnomad AFR exome AF: 0.787

Gnomad AMR exome AF: 0.346

Gnomad ASJ exome AF: 0.432

Gnomad EAS exome AF: 0.166

Gnomad SAS exome AF: 0.483

Gnomad FIN exome AF: 0.309

Gnomad NFE exome AF: 0.412

Gnomad OTH exome AF: 0.440

GnomAD4 exome AF: 0.410 AC: 599837 AN: 1461842 Hom.: 128235 Cov.: 59 AF XY: 0.413 AC XY: 300157 AN XY: 727230

Gnomad4 AFR exome AF: 0.798

Gnomad4 AMR exome AF: 0.360

Gnomad4 ASJ exome AF: 0.425

Gnomad4 EAS exome AF: 0.170

Gnomad4 SAS exome AF: 0.483

Gnomad4 FIN exome AF: 0.306

Gnomad4 NFE exome AF: 0.406

Gnomad4 OTH exome AF: 0.434

GnomAD4 genome AF: 0.501 AC: 76167 AN: 152074 Hom.: 21740 Cov.: 32 AF XY: 0.493 AC XY: 36622 AN XY: 74334

Gnomad4 AFR AF: 0.782

Gnomad4 AMR AF: 0.438

Gnomad4 ASJ AF: 0.418

Gnomad4 EAS AF: 0.164

Gnomad4 SAS AF: 0.467

Gnomad4 FIN AF: 0.301

Gnomad4 NFE AF: 0.408

Gnomad4 OTH AF: 0.496

Alfa AF: 0.433 Hom.: 32578

Bravo AF: 0.523

TwinsUK AF: 0.420 AC: 1556

ALSPAC AF: 0.416 AC: 1605

ESP6500AA AF: 0.774 AC: 3409

ESP6500EA AF: 0.411 AC: 3537

ExAC AF: 0.420 AC: 50951

Asia WGS AF: 0.370 AC: 1286 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.051
BayesDel_addAF	Benign	-0.84	T
BayesDel_noAF	Benign	-0.84
CADD	Benign	12
DANN	Benign	0.95
DEOGEN2	Benign	0.00055	T;.
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.0050	N
LIST_S2	Benign	0.13	T;T
MetaRNN	Benign	0.0000013	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.69	N;.
MutationTaster	Benign	1.0	P
PrimateAI	Benign	0.25	T
PROVEAN	Benign	1.7	N;.
REVEL	Benign	0.054
Sift	Benign	0.64	T;.
Sift4G	Benign	0.29	T;T
Polyphen		0.0	B;.
Vest4		0.018
MPC		0.061
ClinPred		0.0038	T
GERP RS		3.5
Varity_R		0.016
gMVP		0.18

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: rs7984952; hg19: chr13-31231806; COSMIC: COSV54998611;