13-30646969-C-A

Variant names:

• chr13-30646969-C-A
• NM_005800.5:c.1150C>A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_005800.5(USPL1):​c.1150C>A​(p.Pro384Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P384S) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: USPL1 NM_005800.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.04

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
USPL1	NM_005800.5	c.1150C>A	p.Pro384Thr	missense_variant	Exon 7 of 9	ENST00000255304.9	NP_005791.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
USPL1	ENST00000255304.9	c.1150C>A	p.Pro384Thr	missense_variant	Exon 7 of 9	1	NM_005800.5	ENSP00000255304.4
USPL1	ENST00000614860.1	c.163C>A	p.Pro55Thr	missense_variant	Exon 5 of 7	1		ENSP00000480656.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Uncertain	0.073	D
BayesDel_noAF	Benign	-0.13
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.12	T;.
Eigen	Uncertain	0.58
Eigen_PC	Uncertain	0.54
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.85	D;T
M_CAP	Benign	0.022	T
MetaRNN	Uncertain	0.66	D;D
MetaSVM	Uncertain	-0.28	T
MutationAssessor	Uncertain	2.4	M;.
PrimateAI	Benign	0.48	T
PROVEAN	Pathogenic	-6.2	D;.
REVEL	Benign	0.27
Sift	Uncertain	0.0030	D;.
Sift4G	Pathogenic	0.0	D;D
Polyphen		1.0	D;.
Vest4		0.56
MutPred		0.41		Gain of catalytic residue at E385 (P = 0.0013);.;
MVP		0.61
MPC		0.31
ClinPred		0.96	D
GERP RS		4.7
Varity_R		0.64
gMVP		0.54

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr13-31221106;