13-30657641-G-C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_005800.5(USPL1):​c.1564G>C​(p.Ala522Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0182 in 1,614,146 control chromosomes in the GnomAD database, including 345 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 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 0.018 (37 hom., cov: 33)
  • Exomes 𝑓: 0.018 (308 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0028252602).
• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.0184 (2795/152288) while in subpopulation AMR AF = 0.0238 (364/15298). AF 95% confidence interval is 0.0218. There are 37 homozygotes in GnomAd4. There are 1313 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 37 AR gene

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>C	p.Ala522Pro	missense	Exon 9 of 9	NP_005791.3
	USPL1	NM_001321532.2		c.1021G>C	p.Ala341Pro	missense	Exon 8 of 8	NP_001308461.1
	USPL1	NM_001321533.2		c.577G>C	p.Ala193Pro	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>C	p.Ala522Pro	missense	Exon 9 of 9	ENSP00000255304.4	Q5W0Q7-1
	USPL1	ENST00000614860.1	TSL:1	c.577G>C	p.Ala193Pro	missense	Exon 7 of 7	ENSP00000480656.1	Q5W0Q7-2
	USPL1	ENST00000898134.1		c.1564G>C	p.Ala522Pro	missense	Exon 9 of 9	ENSP00000568193.1

Frequencies

GnomAD3 genomes AF: 0.0183 AC: 2792 AN: 152170 Hom.: 37 Cov.: 33

Gnomad AFR AF: 0.0205

Gnomad AMI AF: 0.0439

Gnomad AMR AF: 0.0238

Gnomad ASJ AF: 0.0403

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00746

Gnomad FIN AF: 0.00330

Gnomad MID AF: 0.0478

Gnomad NFE AF: 0.0185

Gnomad OTH AF: 0.0258

GnomAD2 exomes AF: 0.0145 AC: 3647 AN: 251338 AF XY: 0.0145

Gnomad AFR exome AF: 0.0202

Gnomad AMR exome AF: 0.0127

Gnomad ASJ exome AF: 0.0350

Gnomad EAS exome AF: 0.000109

Gnomad FIN exome AF: 0.00268

Gnomad NFE exome AF: 0.0183

Gnomad OTH exome AF: 0.0192

GnomAD4 exome AF: 0.0182 AC: 26546 AN: 1461858 Hom.: 308 Cov.: 30 AF XY: 0.0179 AC XY: 12990 AN XY: 727226

African (AFR) AF: 0.0212 AC: 709 AN: 33480

American (AMR) AF: 0.0134 AC: 600 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0358 AC: 936 AN: 26134

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39694

South Asian (SAS) AF: 0.00865 AC: 746 AN: 86256

European-Finnish (FIN) AF: 0.00232 AC: 124 AN: 53418

Middle Eastern (MID) AF: 0.0302 AC: 174 AN: 5768

European-Non Finnish (NFE) AF: 0.0199 AC: 22106 AN: 1111990

Other (OTH) AF: 0.0190 AC: 1149 AN: 60394

GnomAD4 genome AF: 0.0184 AC: 2795 AN: 152288 Hom.: 37 Cov.: 33 AF XY: 0.0176 AC XY: 1313 AN XY: 74460

African (AFR) AF: 0.0206 AC: 854 AN: 41546

American (AMR) AF: 0.0238 AC: 364 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0403 AC: 140 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00726 AC: 35 AN: 4820

European-Finnish (FIN) AF: 0.00330 AC: 35 AN: 10612

Middle Eastern (MID) AF: 0.0479 AC: 14 AN: 292

European-Non Finnish (NFE) AF: 0.0185 AC: 1259 AN: 68030

Other (OTH) AF: 0.0255 AC: 54 AN: 2116

Alfa AF: 0.0175 Hom.: 17

Bravo AF: 0.0210

TwinsUK AF: 0.0224 AC: 83

ALSPAC AF: 0.0236 AC: 91

ESP6500AA AF: 0.0229 AC: 101

ESP6500EA AF: 0.0200 AC: 172

ExAC AF: 0.0143 AC: 1736

EpiCase AF: 0.0228

EpiControl AF: 0.0216

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.67	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	6.4
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0015	T
Eigen	Benign	-0.93
Eigen_PC	Benign	-0.95
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.43	T
MetaRNN	Benign	0.0028	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	1.2	L
PhyloP100		-0.080
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.040
Sift	Benign	0.40	T
Sift4G	Benign	0.27	T
Polyphen		0.099	B
Vest4		0.047
MPC		0.061
ClinPred		0.0065	T
GERP RS		3.1
Varity_R		0.036
gMVP		0.31
Mutation Taster		=87/13	polymorphism (auto)

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: COSV99079527;