16-84733474-T-C

Variant names:

• chr16-84733474-T-C
• NM_005153.3:c.61T>C
• USP10 p.Phe21Leu

Variant summary

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

The NM_005153.3(USP10):​c.61T>C​(p.Phe21Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: USP10 NM_005153.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.95
• Publications: 0 publications found

Genes affected

USP10 (HGNC:12608): (ubiquitin specific peptidase 10) Ubiquitin is a highly conserved protein that is covalently linked to other proteins to regulate their function and degradation. This gene encodes a member of the ubiquitin-specific protease family of cysteine proteases. The enzyme specifically cleaves ubiquitin from ubiquitin-conjugated protein substrates. The protein is found in the nucleus and cytoplasm. It functions as a co-factor of the DNA-bound androgen receptor complex, and is inhibited by a protein in the Ras-GTPase pathway. The human genome contains several pseudogenes similar to this gene. Several transcript variants, some protein-coding and others not protein-coding, have been found for this gene. [provided by RefSeq, Jan 2013]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005153.3. 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
	USP10	NM_005153.3	MANE Select	c.61T>C	p.Phe21Leu	missense	Exon 2 of 14	NP_005144.2	Q14694-1
	USP10	NM_001272075.2		c.73T>C	p.Phe25Leu	missense	Exon 3 of 15	NP_001259004.1	A0A7G6J4N4
	USP10	NR_073577.2		n.152T>C		non_coding_transcript_exon	Exon 2 of 12

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USP10	ENST00000219473.12	TSL:1 MANE Select	c.61T>C	p.Phe21Leu	missense	Exon 2 of 14	ENSP00000219473.7	Q14694-1
	USP10	ENST00000540269.6	TSL:1	n.61T>C		non_coding_transcript_exon	Exon 2 of 11	ENSP00000445589.2	Q68D90
	USP10	ENST00000933625.1		c.61T>C	p.Phe21Leu	missense	Exon 2 of 14	ENSP00000603684.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.96
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.080	T
Eigen	Pathogenic	0.74
Eigen_PC	Pathogenic	0.72
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.97	D
M_CAP	Benign	0.030	D
MetaRNN	Uncertain	0.59	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		7.0
PrimateAI	Pathogenic	0.87	D
PROVEAN	Uncertain	-2.8	D
REVEL	Uncertain	0.33
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.070	T
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.6
Varity_R		0.42
gMVP		0.60

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr16-84767080;