13-30630867-T-G

Variant names:

• chr13-30630867-T-G
• NM_005800.5:c.261T>G
• USPL1 p.Asn87Lys

Variant summary

Our verdict is

Uncertain significance

0 Uncertain · Cold

-7

-6

-1

0

+5

+6

+9

+10

BenignB

Likely BenignLB

UncertainVUS

Likely PathogenicLP

PathogenicP

. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_005800.5(USPL1):​c.261T>G​(p.Asn87Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: USPL1 NM_005800.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.762
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (REVEL=0.024).

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.261T>G	p.Asn87Lys	missense	Exon 4 of 9	NP_005791.3
	USPL1	NM_001321532.2		c.-283T>G		5_prime_UTR	Exon 3 of 8	NP_001308461.1
	USPL1	NM_001321533.2		c.-119-6877T>G		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.261T>G	p.Asn87Lys	missense	Exon 4 of 9	ENSP00000255304.4	Q5W0Q7-1
	USPL1	ENST00000614860.1	TSL:1	c.-119-6877T>G		intron	N/A	ENSP00000480656.1	Q5W0Q7-2
	USPL1	ENST00000898134.1		c.261T>G	p.Asn87Lys	missense	Exon 4 of 9	ENSP00000568193.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.039	T
Eigen	Benign	-0.41
Eigen_PC	Benign	-0.36
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.45	T
M_CAP	Benign	0.0063	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.5	L
PhyloP100		0.76
PrimateAI	Benign	0.37	T
PROVEAN	Uncertain	-2.8	D
REVEL	Benign	0.024
Sift	Benign	0.039	D
Sift4G	Uncertain	0.049	D
Varity_R		0.089
gMVP		0.25
Mutation Taster		=93/7	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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr13-31205004;

ACMG debug oncogenicity

ACGS debug oncogenicity

ACMG debug germline