rs7183892

Positions:

• chr15-63586733-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006537.4(USP3):​c.1097-1572C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.792 in 152,258 control chromosomes in the GnomAD database, including 49,505 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 0.79 (49502 hom., cov: 33)
  • Exomes 𝑓: 0.88 (3 hom.)
• Consequence: USP3 NM_006537.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.202

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=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.842 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
USP3	NM_006537.4	c.1097-1572C>T		intron_variant		ENST00000380324.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
USP3	ENST00000380324.8	c.1097-1572C>T		intron_variant		1	NM_006537.4	P1
USP3-AS1	ENST00000649220.2	n.571+2096G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.792 AC: 120424 AN: 152132 Hom.: 49449 Cov.: 33

Gnomad AFR AF: 0.838

Gnomad AMI AF: 0.859

Gnomad AMR AF: 0.705

Gnomad ASJ AF: 0.826

Gnomad EAS AF: 0.0865

Gnomad SAS AF: 0.595

Gnomad FIN AF: 0.789

Gnomad MID AF: 0.839

Gnomad NFE AF: 0.848

Gnomad OTH AF: 0.779

GnomAD4 exome AF: 0.875 AC: 7 AN: 8 Hom.: 3 Cov.: 0 AF XY: 0.875 AC XY: 7 AN XY: 8

Gnomad4 ASJ exome AF: 1.00

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 0.750

GnomAD4 genome AF: 0.792 AC: 120531 AN: 152250 Hom.: 49502 Cov.: 33 AF XY: 0.780 AC XY: 58034 AN XY: 74434

Gnomad4 AFR AF: 0.839

Gnomad4 AMR AF: 0.704

Gnomad4 ASJ AF: 0.826

Gnomad4 EAS AF: 0.0864

Gnomad4 SAS AF: 0.596

Gnomad4 FIN AF: 0.789

Gnomad4 NFE AF: 0.848

Gnomad4 OTH AF: 0.781

Alfa AF: 0.826 Hom.: 23999

Bravo AF: 0.783

Asia WGS AF: 0.393 AC: 1369 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.7
DANN	Benign	0.41

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: rs7183892; hg19: chr15-63878932;