NM_006537.4:c.41C>A

Variant names:

• chr15-63504780-C-A
• NM_006537.4:c.41C>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_006537.4(USP3):​c.41C>A​(p.Pro14Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: USP3 NM_006537.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.30
• Publications: 0 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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.29853958).

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.41C>A	p.Pro14Gln	missense	Exon 1 of 15	NP_006528.2	Q9Y6I4-1
	USP3	NM_001256702.2		c.41C>A	p.Pro14Gln	missense	Exon 1 of 14	NP_001243631.1	Q9Y6I4-2
	USP3	NR_046341.2		n.188C>A		non_coding_transcript_exon	Exon 1 of 16

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USP3	ENST00000380324.8	TSL:1 MANE Select	c.41C>A	p.Pro14Gln	missense	Exon 1 of 15	ENSP00000369681.3	Q9Y6I4-1
	USP3	ENST00000558157.5	TSL:1	n.41C>A		non_coding_transcript_exon	Exon 1 of 16	ENSP00000452929.1	H0YNK1
	USP3	ENST00000559192.5	TSL:1	n.41C>A		non_coding_transcript_exon	Exon 1 of 16	ENSP00000453228.1	H0YLJ0

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1459154 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 725942

African (AFR) AF: 0.00 AC: 0 AN: 33200

American (AMR) AF: 0.00 AC: 0 AN: 44564

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26050

East Asian (EAS) AF: 0.00 AC: 0 AN: 39536

South Asian (SAS) AF: 0.00 AC: 0 AN: 85870

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52988

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5682

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111002

Other (OTH) AF: 0.00 AC: 0 AN: 60262

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
CADD	Benign	22
DANN	Benign	0.94
DEOGEN2	Benign	0.0041	T
Eigen	Benign	-0.22
Eigen_PC	Benign	-0.044
FATHMM_MKL	Benign	0.67	D
LIST_S2	Uncertain	0.86	D
M_CAP	Pathogenic	0.99	D
MetaRNN	Benign	0.30	T
MetaSVM	Uncertain	-0.12	T
MutationAssessor	Benign	1.5	L
PhyloP100		3.3
PrimateAI	Pathogenic	0.90	D
PROVEAN	Benign	1.1	N
REVEL	Uncertain	0.40
Sift	Benign	0.53	T
Sift4G	Benign	0.67	T
Polyphen		0.0020	B
Vest4		0.45
MutPred		0.26		Gain of solvent accessibility (P = 0.0365)
MVP		0.70
MPC		0.44
ClinPred		0.75	D
GERP RS		4.7
PromoterAI		-0.029	Neutral
Varity_R		0.12
Mutation Taster		=70/30	polymorphism

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

hg19: chr15-63796979;