chr16-84745002-A-C

Position:

• chr16-84745002-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005153.3(USP10):​c.521A>C​(p.Glu174Ala) 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. 15/21 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: USP10 NM_005153.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.56

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07586467).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
USP10	NM_005153.3	c.521A>C	p.Glu174Ala	missense_variant	4/14	ENST00000219473.12	NP_005144.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
USP10	ENST00000219473.12	c.521A>C	p.Glu174Ala	missense_variant	4/14	1	NM_005153.3	ENSP00000219473	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 20, 2024

The c.521A>C (p.E174A) alteration is located in exon 4 (coding exon 4) of the USP10 gene. This alteration results from a A to C substitution at nucleotide position 521, causing the glutamic acid (E) at amino acid position 174 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	15
DANN	Benign	0.89
DEOGEN2	Benign	0.0094	T;.
Eigen	Benign	-0.88
Eigen_PC	Benign	-0.85
FATHMM_MKL	Benign	0.21	N
LIST_S2	Benign	0.75	T;T
M_CAP	Benign	0.0023	T
MetaRNN	Benign	0.076	T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.6	L;.
MutationTaster	Benign	0.93	N;N
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-2.1	N;N
REVEL	Benign	0.072
Sift	Benign	0.35	T;T
Sift4G	Benign	0.35	T;T
Polyphen		0.0	B;B
Vest4		0.17
MutPred		0.31		Loss of catalytic residue at E174 (P = 0.0616);.;
MVP		0.17
MPC		0.057
ClinPred		0.10	T
GERP RS		1.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.043
gMVP		0.17

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: chr16-84778608;