15-63586733-C-T

Variant names:

• chr15-63586733-C-T
• rs7183892
• NM_006537.4:c.1097-1572C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 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=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.842 is higher than 0.05.

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.1097-1572C>T		intron	N/A	NP_006528.2	Q9Y6I4-1
	USP3	NM_001256702.2		c.965-1572C>T		intron	N/A	NP_001243631.1	Q9Y6I4-2
	USP3	NR_046341.2		n.1397-1572C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USP3	ENST00000380324.8	TSL:1 MANE Select	c.1097-1572C>T		intron	N/A	ENSP00000369681.3	Q9Y6I4-1
	USP3	ENST00000558285.5	TSL:1	c.1046-1572C>T		intron	N/A	ENSP00000453619.1	H0YMI4
	USP3	ENST00000538686.6	TSL:1	n.*950-1572C>T		intron	N/A	ENSP00000445793.2

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 2 AN: 2

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 1.00 AC: 2 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.750 AC: 3 AN: 4

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.839 AC: 34846 AN: 41544

American (AMR) AF: 0.704 AC: 10757 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.826 AC: 2868 AN: 3472

East Asian (EAS) AF: 0.0864 AC: 447 AN: 5176

South Asian (SAS) AF: 0.596 AC: 2871 AN: 4820

European-Finnish (FIN) AF: 0.789 AC: 8372 AN: 10606

Middle Eastern (MID) AF: 0.840 AC: 247 AN: 294

European-Non Finnish (NFE) AF: 0.848 AC: 57691 AN: 68026

Other (OTH) AF: 0.781 AC: 1650 AN: 2114

Alfa AF: 0.819 Hom.: 91174

Bravo AF: 0.783

Asia WGS AF: 0.393 AC: 1369 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.7
DANN	Benign	0.41
PhyloP100		0.20
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: rs7183892; hg19: chr15-63878932;