13-30630870-C-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_005800.5(USPL1):​c.264C>T​(p.Asn88Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000959 in 1,460,284 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000096 (0 hom.)
• Consequence: USPL1 NM_005800.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.137
• 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 -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BP7: Synonymous conserved (PhyloP=-0.137 with no splicing effect.

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.264C>T	p.Asn88Asn	synonymous	Exon 4 of 9	NP_005791.3
	USPL1	NM_001321532.2		c.-280C>T		5_prime_UTR	Exon 3 of 8	NP_001308461.1
	USPL1	NM_001321533.2		c.-119-6874C>T		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.264C>T	p.Asn88Asn	synonymous	Exon 4 of 9	ENSP00000255304.4	Q5W0Q7-1
	USPL1	ENST00000614860.1	TSL:1	c.-119-6874C>T		intron	N/A	ENSP00000480656.1	Q5W0Q7-2
	USPL1	ENST00000898134.1		c.264C>T	p.Asn88Asn	synonymous	Exon 4 of 9	ENSP00000568193.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000280 AC: 7 AN: 250092 AF XY: 0.0000222

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: 0.00

Gnomad NFE exome AF: 0.0000618

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000959 AC: 14 AN: 1460284 Hom.: 0 Cov.: 31 AF XY: 0.00000964 AC XY: 7 AN XY: 726416

African (AFR) AF: 0.0000300 AC: 1 AN: 33292

American (AMR) AF: 0.00 AC: 0 AN: 44416

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26104

East Asian (EAS) AF: 0.00 AC: 0 AN: 39668

South Asian (SAS) AF: 0.00 AC: 0 AN: 85906

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53378

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00000900 AC: 10 AN: 1111462

Other (OTH) AF: 0.0000498 AC: 3 AN: 60294

GnomAD4 genome Cov.: 32

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	1.3
DANN	Benign	0.40
PhyloP100		-0.14

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs372178207; hg19: chr13-31205007; COSMIC: COSV104547572;