rs146583283

Variant names:

• chr15-63588415-C-T
• rs146583283
• NM_006537.4:c.1207C>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 0P and 3B. BP4 BP6_Moderate

The NM_006537.4(USP3):​c.1207C>T​(p.Leu403Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00026 in 1,601,428 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00015 (0 hom.)
• Consequence: USP3 NM_006537.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.28
• Publications: 1 publications found

Genes affected

USP3 (HGNC:12626): (ubiquitin specific peptidase 3) Enables histone binding activity and thiol-dependent deubiquitinase. Involved in several processes, including DNA repair; histone deubiquitination; and regulation of protein stability. Located in several cellular components, including Flemming body; cytoplasmic ribonucleoprotein granule; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

USP3-AS1 (HGNC:44140): (USP3 antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.18).
• BP6: Variant 15-63588415-C-T is Benign according to our data. Variant chr15-63588415-C-T is described in ClinVar as Benign. ClinVar VariationId is 712841.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006537.4. 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
	USP3	NM_006537.4	MANE Select	c.1207C>T	p.Leu403Leu	synonymous	Exon 12 of 15	NP_006528.2	Q9Y6I4-1
	USP3	NM_001256702.2		c.1075C>T	p.Leu359Leu	synonymous	Exon 11 of 14	NP_001243631.1	Q9Y6I4-2
	USP3-AS1	NR_034080.1		n.1017G>A		non_coding_transcript_exon	Exon 3 of 3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USP3	ENST00000380324.8	TSL:1 MANE Select	c.1207C>T	p.Leu403Leu	synonymous	Exon 12 of 15	ENSP00000369681.3	Q9Y6I4-1
	USP3	ENST00000558285.5	TSL:1	c.1156C>T	p.Leu386Leu	synonymous	Exon 11 of 14	ENSP00000453619.1	H0YMI4
	USP3	ENST00000538686.6	TSL:1	n.*1060C>T		non_coding_transcript_exon	Exon 11 of 14	ENSP00000445793.2

Frequencies

GnomAD3 genomes AF: 0.00131 AC: 199 AN: 152200 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00449

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000393

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: 0.0000147

Gnomad OTH AF: 0.00287

GnomAD2 exomes AF: 0.000385 AC: 92 AN: 238714 AF XY: 0.000348

Gnomad AFR exome AF: 0.00577

Gnomad AMR exome AF: 0.0000316

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000150 AC: 217 AN: 1449110 Hom.: 0 Cov.: 30 AF XY: 0.000153 AC XY: 110 AN XY: 720948

African (AFR) AF: 0.00616 AC: 201 AN: 32620

American (AMR) AF: 0.0000241 AC: 1 AN: 41452

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25672

East Asian (EAS) AF: 0.00 AC: 0 AN: 39600

South Asian (SAS) AF: 0.00 AC: 0 AN: 83622

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53206

Middle Eastern (MID) AF: 0.000175 AC: 1 AN: 5706

European-Non Finnish (NFE) AF: 0.00000181 AC: 2 AN: 1107360

Other (OTH) AF: 0.000200 AC: 12 AN: 59872

GnomAD4 genome AF: 0.00131 AC: 199 AN: 152318 Hom.: 0 Cov.: 32 AF XY: 0.00125 AC XY: 93 AN XY: 74478

African (AFR) AF: 0.00447 AC: 186 AN: 41578

American (AMR) AF: 0.000392 AC: 6 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68030

Other (OTH) AF: 0.00284 AC: 6 AN: 2112

Alfa AF: 0.000979 Hom.: 1

Bravo AF: 0.00176

Asia WGS AF: 0.000578 AC: 2 AN: 3476

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.18
CADD	Benign	11
DANN	Benign	0.81
PhyloP100		3.3
Mutation Taster		=97/3	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

Other links and lift over

dbSNP: rs146583283; hg19: chr15-63880614;