13-30631009-A-C

Variant names:

• chr13-30631009-A-C
• NM_005800.5:c.403A>C
• USPL1 p.Lys135Gln

Variant summary

Our verdict is

Likely benign

-2 Likely Benign

-7

-6

-1

0

+5

+6

+9

+10

BenignB

Likely BenignLB

UncertainVUS

Likely PathogenicLP

PathogenicP

. The variant received -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate

The NM_005800.5(USPL1):​c.403A>C​(p.Lys135Gln) 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. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: USPL1 NM_005800.5 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.638
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (REVEL=0.041).
• BP6: Variant 13-30631009-A-C is Benign according to our data. Variant chr13-30631009-A-C is described in ClinVar as Likely_benign. ClinVar VariationId is 3467357.Status of the report is criteria_provided_single_submitter, 1 stars.

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.403A>C	p.Lys135Gln	missense	Exon 4 of 9	NP_005791.3
	USPL1	NM_001321532.2		c.-141A>C		5_prime_UTR	Exon 3 of 8	NP_001308461.1
	USPL1	NM_001321533.2		c.-119-6735A>C		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.403A>C	p.Lys135Gln	missense	Exon 4 of 9	ENSP00000255304.4	Q5W0Q7-1
	USPL1	ENST00000614860.1	TSL:1	c.-119-6735A>C		intron	N/A	ENSP00000480656.1	Q5W0Q7-2
	USPL1	ENST00000898134.1		c.403A>C	p.Lys135Gln	missense	Exon 4 of 9	ENSP00000568193.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Likely benign

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	0.069
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.2
DANN	Benign	0.12
DEOGEN2	Benign	0.0016	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.0060	N
LIST_S2	Benign	0.55	T
M_CAP	Benign	0.0021	T
MetaRNN	Benign	0.031	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	-2.0	N
PhyloP100		0.64
PrimateAI	Benign	0.24	T
PROVEAN	Benign	1.9	N
REVEL	Benign	0.041
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Varity_R		0.037
gMVP		0.17
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

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

Other links and lift over

hg19: chr13-31205146;

ACMG debug oncogenicity

ACGS debug oncogenicity

ACMG debug germline