rs10450989

Variant names:

• chr15-63554309-T-C
• rs10450989
• NM_006537.4:c.368+511T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_006537.4(USP3):​c.368+511T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.033 in 152,298 control chromosomes in the GnomAD database, including 106 homozygotes. 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: 𝑓 0.033 (106 hom., cov: 32)
• Consequence: USP3 NM_006537.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0730
• Publications: 7 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.033 (5022/152298) while in subpopulation NFE AF = 0.0466 (3171/68010). AF 95% confidence interval is 0.0453. There are 106 homozygotes in GnomAd4. There are 2499 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 106 gene

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USP3	NM_006537.4	MANE Select	c.368+511T>C		intron	N/A	NP_006528.2
	USP3	NM_001256702.2		c.236+511T>C		intron	N/A	NP_001243631.1
	USP3	NR_046341.2		n.668+511T>C		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USP3	ENST00000380324.8	TSL:1 MANE Select	c.368+511T>C		intron	N/A	ENSP00000369681.3
	USP3	ENST00000558285.5	TSL:1	c.317+511T>C		intron	N/A	ENSP00000453619.1
	USP3	ENST00000538686.6	TSL:1	n.*221+511T>C		intron	N/A	ENSP00000445793.2

Frequencies

GnomAD3 genomes AF: 0.0330 AC: 5017 AN: 152180 Hom.: 106 Cov.: 32

Gnomad AFR AF: 0.00791

Gnomad AMI AF: 0.0132

Gnomad AMR AF: 0.0352

Gnomad ASJ AF: 0.0340

Gnomad EAS AF: 0.00134

Gnomad SAS AF: 0.0428

Gnomad FIN AF: 0.0492

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.0466

Gnomad OTH AF: 0.0402

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0330 AC: 5022 AN: 152298 Hom.: 106 Cov.: 32 AF XY: 0.0336 AC XY: 2499 AN XY: 74472

African (AFR) AF: 0.00808 AC: 336 AN: 41578

American (AMR) AF: 0.0351 AC: 537 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0340 AC: 118 AN: 3472

East Asian (EAS) AF: 0.00135 AC: 7 AN: 5194

South Asian (SAS) AF: 0.0428 AC: 207 AN: 4832

European-Finnish (FIN) AF: 0.0492 AC: 521 AN: 10596

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.0466 AC: 3171 AN: 68010

Other (OTH) AF: 0.0397 AC: 84 AN: 2114

Alfa AF: 0.0437 Hom.: 282

Bravo AF: 0.0299

Asia WGS AF: 0.0220 AC: 77 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.0
DANN	Benign	0.63
PhyloP100		-0.073
Mutation Taster		=100/0	polymorphism (auto)

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: rs10450989; hg19: chr15-63846508;