16-84733476-C-T

Variant names:

• chr16-84733476-C-T
• rs1286466190
• NM_005153.3:c.63C>T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_005153.3(USP10):​c.63C>T​(p.Phe21Phe) variant causes a synonymous 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: USP10 NM_005153.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.55
• Publications: 1 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: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.34).
• BP7: Synonymous conserved (PhyloP=1.55 with no splicing effect.

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.63C>T	p.Phe21Phe	synonymous	Exon 2 of 14	NP_005144.2	Q14694-1
	USP10	NM_001272075.2		c.75C>T	p.Phe25Phe	synonymous	Exon 3 of 15	NP_001259004.1	A0A7G6J4N4
	USP10	NR_073577.2		n.154C>T		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.63C>T	p.Phe21Phe	synonymous	Exon 2 of 14	ENSP00000219473.7	Q14694-1
	USP10	ENST00000540269.6	TSL:1	n.63C>T		non_coding_transcript_exon	Exon 2 of 11	ENSP00000445589.2	Q68D90
	USP10	ENST00000933625.1		c.63C>T	p.Phe21Phe	synonymous	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	Benign	0.18
BayesDel_noAF	Benign	-0.34
CADD	Benign	11
DANN	Benign	0.93
PhyloP100		1.6

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: rs1286466190; hg19: chr16-84767082;