17-5133982-T-G

Variant names:

• chr17-5133982-T-G
• rs747703023
• NM_001304284.2:c.480T>G

Variant summary

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

The NM_001304284.2(USP6):​c.480T>G​(p.Asp160Glu) 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. 14/21 in silico tools predict 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: 31)
• Consequence: USP6 NM_001304284.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.661

Genes affected

USP6 (HGNC:12629): (ubiquitin specific peptidase 6) Enables thiol-dependent deubiquitinase. Involved in protein deubiquitination and regulation of vesicle-mediated transport. Located in plasma membrane and recycling endosome. [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=0.17179114).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
USP6	NM_001304284.2	c.480T>G	p.Asp160Glu	missense_variant	Exon 15 of 38	ENST00000574788.6	NP_001291213.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
USP6	ENST00000574788.6	c.480T>G	p.Asp160Glu	missense_variant	Exon 15 of 38	1	NM_001304284.2	ENSP00000460380.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	9.8
DANN	Benign	0.65
DEOGEN2	Benign	0.0031	T;T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.092	N
LIST_S2	Benign	0.34	.;T
M_CAP	Benign	0.0049	T
MetaRNN	Benign	0.17	T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	0.47	N;N
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-0.71	.;N
REVEL	Benign	0.14
Sift	Benign	0.31	.;T
Sift4G	Benign	0.57	T;T
Polyphen		0.72	P;P
Vest4		0.35
MutPred		0.34		Loss of MoRF binding (P = 0.1113);Loss of MoRF binding (P = 0.1113);
MVP		0.20
MPC		0.63
ClinPred		0.59	D
GERP RS		-1.7
Varity_R		0.085
gMVP		0.44

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs747703023; hg19: chr17-5037277;