rs10450989

Positions:

• chr15-63554309-T-C

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 106 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
USP3	NM_006537.4	c.368+511T>C		intron_variant		ENST00000380324.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
USP3	ENST00000380324.8	c.368+511T>C		intron_variant		1	NM_006537.4	P1
USP3-AS1	ENST00000649220.2	n.3019A>G		non_coding_transcript_exon_variant	5/5

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

Gnomad4 AFR AF: 0.00808

Gnomad4 AMR AF: 0.0351

Gnomad4 ASJ AF: 0.0340

Gnomad4 EAS AF: 0.00135

Gnomad4 SAS AF: 0.0428

Gnomad4 FIN AF: 0.0492

Gnomad4 NFE AF: 0.0466

Gnomad4 OTH AF: 0.0397

Alfa AF: 0.0456 Hom.: 235

Bravo AF: 0.0299

Asia WGS AF: 0.0220 AC: 77 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.0
DANN	Benign	0.63

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: rs10450989; hg19: chr15-63846508;