17-5133514-T-G

Position:

• chr17-5133514-T-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.348T>G​(p.Ile116Met) 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. 12/21 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: USP6 NM_001304284.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.65

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]

USP6 (HGNC:):

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=0.22415489).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
USP6	NM_001304284.2	c.348T>G	p.Ile116Met	missense_variant	14/38	ENST00000574788.6	NP_001291213.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
USP6	ENST00000574788.6	c.348T>G	p.Ile116Met	missense_variant	14/38	1	NM_001304284.2	ENSP00000460380.1

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

Oct 27, 2021

The c.348T>G (p.I116M) alteration is located in exon 6 (coding exon 5) of the USP6 gene. This alteration results from a T to G substitution at nucleotide position 348, causing the isoleucine (I) at amino acid position 116 to be replaced by a methionine (M). 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	0.30
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	11
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0066	T;T
Eigen	Benign	-0.40
Eigen_PC	Benign	-0.65
FATHMM_MKL	Benign	0.011	N
LIST_S2	Benign	0.75	.;T
M_CAP	Benign	0.0021	T
MetaRNN	Benign	0.22	T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Uncertain	2.5	M;M
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-0.97	.;N
REVEL	Benign	0.12
Sift	Uncertain	0.0030	.;D
Sift4G	Uncertain	0.0040	D;D
Polyphen		0.96	P;P
Vest4		0.27
MutPred		0.61		Gain of catalytic residue at V112 (P = 0.0499);Gain of catalytic residue at V112 (P = 0.0499);
MVP		0.52
MPC		0.60
ClinPred		0.85	D
GERP RS		-0.60
Varity_R		0.35
gMVP		0.51

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: chr17-5036809;