chr15-63532660-C-A

Variant names:

• chr15-63532660-C-A
• NM_006537.4:c.105C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006537.4(USP3):​c.105C>A​(p.Asn35Lys) 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. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: USP3 NM_006537.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.71
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.25439954).

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.105C>A	p.Asn35Lys	missense	Exon 2 of 15	NP_006528.2	Q9Y6I4-1
	USP3	NM_001256702.2		c.105C>A	p.Asn35Lys	missense	Exon 2 of 14	NP_001243631.1	Q9Y6I4-2
	USP3	NR_046341.2		n.405C>A		non_coding_transcript_exon	Exon 3 of 16

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USP3	ENST00000380324.8	TSL:1 MANE Select	c.105C>A	p.Asn35Lys	missense	Exon 2 of 15	ENSP00000369681.3	Q9Y6I4-1
	USP3	ENST00000558285.5	TSL:1	c.54C>A	p.Asn18Lys	missense	Exon 1 of 14	ENSP00000453619.1	H0YMI4
	USP3	ENST00000558157.5	TSL:1	n.*87C>A		non_coding_transcript_exon	Exon 3 of 16	ENSP00000452929.1	H0YNK1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

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	Pathogenic	0.81
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.014	T
Eigen	Benign	0.17
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.0081	T
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.73	N
PhyloP100		2.7
PrimateAI	Pathogenic	0.92	D
PROVEAN	Benign	-0.38	N
REVEL	Benign	0.14
Sift	Benign	0.30	T
Sift4G	Benign	0.68	T
Polyphen		0.54	P
Vest4		0.59
MutPred		0.60		Gain of methylation at N35 (P = 0.0086)
MVP		0.21
MPC		1.5
ClinPred		0.59	D
GERP RS		6.2
PromoterAI		-0.016	Neutral
Varity_R		0.35

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr15-63824859;