rs139639201

Variant names:

• chr15-63588763-C-A
• NM_006537.4:c.1277C>A

Your query was ambiguous. Multiple possible variants found:

• chr15-63588763-C-A
• chr15-63588763-C-G
• chr15-63588763-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_006537.4(USP3):​c.1277C>A​(p.Thr426Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,856 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T426I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: USP3 NM_006537.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.10

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
USP3	NM_006537.4	c.1277C>A	p.Thr426Lys	missense_variant	Exon 13 of 15	ENST00000380324.8	NP_006528.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
USP3	ENST00000380324.8	c.1277C>A	p.Thr426Lys	missense_variant	Exon 13 of 15	1	NM_006537.4	ENSP00000369681.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461856 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727234

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.96
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.020
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.13	.;T;T;T;.
Eigen	Uncertain	0.52
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.94	D;D;D;D;D
M_CAP	Benign	0.020	T
MetaRNN	Uncertain	0.72	D;D;D;D;D
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	.;L;.;.;.
PrimateAI	Pathogenic	0.81	D
PROVEAN	Uncertain	-3.6	D;D;D;D;D
REVEL	Benign	0.28
Sift	Uncertain	0.011	D;D;D;D;D
Sift4G	Uncertain	0.028	D;D;D;D;D
Polyphen		1.0	.;D;D;.;.
Vest4		0.81
MutPred		0.67		.;Gain of ubiquitination at T426 (P = 0.0276);.;.;.;
MVP		0.35
MPC		1.5
ClinPred		0.99	D
GERP RS		4.5
Varity_R		0.66

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr15-63880962;