chr13-30631034-G-A

Variant names:

• chr13-30631034-G-A
• rs146374694
• NM_005800.5:c.428G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_005800.5(USPL1):​c.428G>A​(p.Gly143Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000271 in 1,614,108 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00025 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00027 (0 hom.)
• Consequence: USPL1 NM_005800.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.450
• Publications: 3 publications found

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

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0064019263).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005800.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USPL1	NM_005800.5	MANE Select	c.428G>A	p.Gly143Glu	missense	Exon 4 of 9	NP_005791.3
	USPL1	NM_001321532.2		c.-116G>A		5_prime_UTR	Exon 3 of 8	NP_001308461.1
	USPL1	NM_001321533.2		c.-119-6710G>A		intron	N/A	NP_001308462.1	Q5W0Q7-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USPL1	ENST00000255304.9	TSL:1 MANE Select	c.428G>A	p.Gly143Glu	missense	Exon 4 of 9	ENSP00000255304.4	Q5W0Q7-1
	USPL1	ENST00000614860.1	TSL:1	c.-119-6710G>A		intron	N/A	ENSP00000480656.1	Q5W0Q7-2
	USPL1	ENST00000898134.1		c.428G>A	p.Gly143Glu	missense	Exon 4 of 9	ENSP00000568193.1

Frequencies

GnomAD3 genomes AF: 0.000250 AC: 38 AN: 152178 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000655

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000220

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000438 AC: 110 AN: 250858 AF XY: 0.000347

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00150

Gnomad ASJ exome AF: 0.00139

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000463

Gnomad NFE exome AF: 0.000291

Gnomad OTH exome AF: 0.00164

GnomAD4 exome AF: 0.000273 AC: 399 AN: 1461812 Hom.: 0 Cov.: 31 AF XY: 0.000253 AC XY: 184 AN XY: 727210

African (AFR) AF: 0.000149 AC: 5 AN: 33480

American (AMR) AF: 0.00150 AC: 67 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00176 AC: 46 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.0000375 AC: 2 AN: 53356

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.000226 AC: 251 AN: 1112008

Other (OTH) AF: 0.000464 AC: 28 AN: 60394

GnomAD4 genome AF: 0.000250 AC: 38 AN: 152296 Hom.: 0 Cov.: 32 AF XY: 0.000215 AC XY: 16 AN XY: 74474

African (AFR) AF: 0.000144 AC: 6 AN: 41560

American (AMR) AF: 0.000654 AC: 10 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00202 AC: 7 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000220 AC: 15 AN: 68028

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.000297 Hom.: 0

Bravo AF: 0.000283

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.000465 AC: 4

ExAC AF: 0.000502 AC: 61

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.000436

EpiControl AF: 0.000296

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.60	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	14
DANN	Benign	0.95
DEOGEN2	Benign	0.036	T
Eigen	Benign	-0.67
Eigen_PC	Benign	-0.62
FATHMM_MKL	Benign	0.30	N
LIST_S2	Benign	0.67	T
M_CAP	Benign	0.0041	T
MetaRNN	Benign	0.0064	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.3	L
PhyloP100		0.45
PrimateAI	Benign	0.24	T
PROVEAN	Uncertain	-3.8	D
REVEL	Benign	0.027
Sift	Benign	0.034	D
Sift4G	Benign	0.22	T
Polyphen		0.096	B
Vest4		0.16
MVP		0.24
MPC		0.088
ClinPred		0.029	T
GERP RS		0.88
Varity_R		0.16
gMVP		0.16
Mutation Taster		=96/4	polymorphism

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

Other links and lift over

dbSNP: rs146374694; hg19: chr13-31205171;