rs17609459

Variant names:

• chr13-30657641-G-A
• rs17609459
• NM_005800.5:c.1564G>A

Your query was ambiguous. Multiple possible variants found:

• chr13-30657641-G-A
• chr13-30657641-G-C
• chr13-30657641-G-T

Variant summary

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

The NM_005800.5(USPL1):​c.1564G>A​(p.Ala522Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000756 in 1,614,160 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000082 (0 hom.)
• Consequence: USPL1 NM_005800.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0800
• Publications: 10 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=0.029517889).

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.1564G>A	p.Ala522Thr	missense	Exon 9 of 9	NP_005791.3
	USPL1	NM_001321532.2		c.1021G>A	p.Ala341Thr	missense	Exon 8 of 8	NP_001308461.1
	USPL1	NM_001321533.2		c.577G>A	p.Ala193Thr	missense	Exon 7 of 7	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.1564G>A	p.Ala522Thr	missense	Exon 9 of 9	ENSP00000255304.4	Q5W0Q7-1
	USPL1	ENST00000614860.1	TSL:1	c.577G>A	p.Ala193Thr	missense	Exon 7 of 7	ENSP00000480656.1	Q5W0Q7-2
	USPL1	ENST00000898134.1		c.1564G>A	p.Ala522Thr	missense	Exon 9 of 9	ENSP00000568193.1

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152174 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000676 AC: 17 AN: 251338 AF XY: 0.0000589

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000707

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000264

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.0000821 AC: 120 AN: 1461868 Hom.: 0 Cov.: 30 AF XY: 0.0000701 AC XY: 51 AN XY: 727234

African (AFR) AF: 0.0000299 AC: 1 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00186 AC: 74 AN: 39694

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

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

European-Non Finnish (NFE) AF: 0.0000351 AC: 39 AN: 1112000

Other (OTH) AF: 0.0000828 AC: 5 AN: 60394

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152292 Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2 AN XY: 74462

African (AFR) AF: 0.00 AC: 0 AN: 41550

American (AMR) AF: 0.00 AC: 0 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68030

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

Alfa AF: 0.00000866 Hom.: 17

ExAC AF: 0.0000659 AC: 8

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.56	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	1.2
DANN	Benign	0.69
DEOGEN2	Benign	0.00082	T
Eigen	Benign	-0.79
Eigen_PC	Benign	-0.86
FATHMM_MKL	Benign	0.22	N
LIST_S2	Benign	0.44	T
M_CAP	Benign	0.0084	T
MetaRNN	Benign	0.030	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.0	L
PhyloP100		-0.080
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.071
Sift	Benign	0.54	T
Sift4G	Benign	0.91	T
Polyphen		0.90	P
Vest4		0.046
MutPred		0.15		Gain of catalytic residue at L523 (P = 2e-04)
MVP		0.22
MPC		0.047
ClinPred		0.040	T
GERP RS		3.1
Varity_R		0.014
gMVP		0.27
Mutation Taster		=98/2	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: rs17609459; hg19: chr13-31231778; COSMIC: COSV55001900;