17-60181401-G-A

Position:

• chr17-60181401-G-A

Variant summary

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

The NM_032582.4(USP32):​c.4471C>T​(p.His1491Tyr) 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: USP32 NM_032582.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.11

Genes affected

USP32 (HGNC:19143): (ubiquitin specific peptidase 32) Enables thiol-dependent deubiquitinase. Predicted to be involved in protein deubiquitination. Located in Golgi apparatus and cytosol. [provided by Alliance of Genome Resources, Apr 2022]

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=0.08921373).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
USP32	NM_032582.4	c.4471C>T	p.His1491Tyr	missense_variant	32/34	ENST00000300896.9	NP_115971.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
USP32	ENST00000300896.9	c.4471C>T	p.His1491Tyr	missense_variant	32/34	1	NM_032582.4	ENSP00000300896.3
USP32	ENST00000592339.5	c.3481C>T	p.His1161Tyr	missense_variant	24/26	1		ENSP00000467885.1
USP32	ENST00000593071.1	c.271C>T	p.His91Tyr	missense_variant	1/2	5		ENSP00000466740.1

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 06, 2023

The c.4471C>T (p.H1491Y) alteration is located in exon 32 (coding exon 32) of the USP32 gene. This alteration results from a C to T substitution at nucleotide position 4471, causing the histidine (H) at amino acid position 1491 to be replaced by a tyrosine (Y). 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	0.066
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.020	T;.
Eigen	Benign	-0.34
Eigen_PC	Benign	-0.10
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.79	T;T
M_CAP	Benign	0.0050	T
MetaRNN	Benign	0.089	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	L;.
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-1.0	N;.
REVEL	Benign	0.064
Sift	Benign	0.38	T;.
Sift4G	Benign	0.87	T;T
Polyphen		0.0	B;.
Vest4		0.28
MutPred		0.40		Gain of phosphorylation at H1491 (P = 0.0247);.;
MVP		0.13
MPC		0.64
ClinPred		0.21	T
GERP RS		4.4
Varity_R		0.096
gMVP		0.32

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: chr17-58258762; COSMIC: COSV100341475; COSMIC: COSV100341475;