13-30630870-C-A

Variant names:

• chr13-30630870-C-A
• rs372178207
• NM_005800.5:c.264C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_005800.5(USPL1):​c.264C>A​(p.Asn88Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000881 in 1,612,428 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/23 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00011 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000086 (0 hom.)
• Consequence: USPL1 NM_005800.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.137

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.

• BP4: Computational evidence support a benign effect (MetaRNN=0.09836498).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
USPL1	NM_005800.5	c.264C>A	p.Asn88Lys	missense_variant	Exon 4 of 9	ENST00000255304.9	NP_005791.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
USPL1	ENST00000255304.9	c.264C>A	p.Asn88Lys	missense_variant	Exon 4 of 9	1	NM_005800.5	ENSP00000255304.4
USPL1	ENST00000614860.1	c.-119-6874C>A		intron_variant	Intron 2 of 6	1		ENSP00000480656.1
USPL1	ENST00000465952.5	n.529C>A		non_coding_transcript_exon_variant	Exon 3 of 3	2

Frequencies

GnomAD3 genomes AF: 0.000105 AC: 16 AN: 152144 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000235

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000104 AC: 26 AN: 250092 AF XY: 0.000104

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000927

Gnomad NFE exome AF: 0.000212

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000863 AC: 126 AN: 1460284 Hom.: 0 Cov.: 31 AF XY: 0.0000977 AC XY: 71 AN XY: 726416

Gnomad4 AFR exome AF: 0.00 AC: 0 AN: 33292

Gnomad4 AMR exome AF: 0.00 AC: 0 AN: 44416

Gnomad4 ASJ exome AF: 0.0000383 AC: 1 AN: 26104

Gnomad4 EAS exome AF: 0.00 AC: 0 AN: 39668

Gnomad4 SAS exome AF: 0.00 AC: 0 AN: 85906

Gnomad4 FIN exome AF: 0.0000562 AC: 3 AN: 53378

Gnomad4 NFE exome AF: 0.000105 AC: 117 AN: 1111462

Gnomad4 Remaining exome AF: 0.0000829 AC: 5 AN: 60294

GnomAD4 genome AF: 0.000105 AC: 16 AN: 152144 Hom.: 0 Cov.: 32 AF XY: 0.000108 AC XY: 8 AN XY: 74322

Gnomad4 AFR AF: 0.00 AC: 0 AN: 0

Gnomad4 AMR AF: 0.00 AC: 0 AN: 0

Gnomad4 ASJ AF: 0.00 AC: 0 AN: 0

Gnomad4 EAS AF: 0.00 AC: 0 AN: 0

Gnomad4 SAS AF: 0.00 AC: 0 AN: 0

Gnomad4 FIN AF: 0.00 AC: 0 AN: 0

Gnomad4 NFE AF: 0.000235 AC: 0.000235197 AN: 0.000235197

Gnomad4 OTH AF: 0.00 AC: 0 AN: 0

Alfa AF: 0.000184 Hom.: 0

Bravo AF: 0.0000869

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.0000988 AC: 12

EpiCase AF: 0.000273

EpiControl AF: 0.000178

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 07, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.264C>A (p.N88K) alteration is located in exon 4 (coding exon 3) of the USPL1 gene. This alteration results from a C to A substitution at nucleotide position 264, causing the asparagine (N) at amino acid position 88 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.57	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	9.3
DANN	Uncertain	0.98
DEOGEN2	Benign	0.011	T
Eigen	Benign	-0.75
Eigen_PC	Benign	-0.89
FATHMM_MKL	Benign	0.32	N
LIST_S2	Benign	0.62	T
M_CAP	Benign	0.0036	T
MetaRNN	Benign	0.098	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	L
PrimateAI	Benign	0.42	T
PROVEAN	Uncertain	-2.5	N
REVEL	Benign	0.036
Sift	Benign	0.10	T
Sift4G	Benign	0.20	T
Polyphen		0.71	P
Vest4		0.29
MutPred		0.39		Gain of solvent accessibility (P = 0.0038);
MVP		0.23
MPC		0.097
ClinPred		0.079	T
GERP RS		-2.1
Varity_R		0.074
gMVP		0.22
Mutation Taster		=99/1	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

Publications

LitVar

Other links and lift over

dbSNP: rs372178207; hg19: chr13-31205007;