17-5132967-G-A

Variant names:

• chr17-5132967-G-A
• rs1244661493
• NM_001304284.2:c.253G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001304284.2(USP6):​c.253G>A​(p.Glu85Lys) variant causes a missense change. 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E85Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: USP6 NM_001304284.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.61
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1376169).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001304284.2. 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
	USP6	NM_001304284.2	MANE Select	c.253G>A	p.Glu85Lys	missense	Exon 13 of 38	NP_001291213.1	P35125-1
	USP6	NM_004505.4		c.253G>A	p.Glu85Lys	missense	Exon 5 of 30	NP_004496.2	P35125-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USP6	ENST00000574788.6	TSL:1 MANE Select	c.253G>A	p.Glu85Lys	missense	Exon 13 of 38	ENSP00000460380.1	P35125-1
	USP6	ENST00000250066.6	TSL:1	c.253G>A	p.Glu85Lys	missense	Exon 5 of 30	ENSP00000250066.6	P35125-1
	USP6	ENST00000357482.5	TSL:1	n.699G>A		non_coding_transcript_exon	Exon 6 of 8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.36
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	11
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0050	T
Eigen	Benign	-0.83
Eigen_PC	Benign	-0.93
FATHMM_MKL	Benign	0.28	N
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.0056	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		3.6
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.048
Sift	Uncertain	0.015	D
Sift4G	Uncertain	0.044	D
Polyphen		0.35	B
Vest4		0.12
MutPred		0.52		Gain of MoRF binding (P = 0.0066)
MVP		0.34
MPC		0.41
ClinPred		0.75	D
GERP RS		0.046
Varity_R		0.15
gMVP		0.42

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: rs1244661493; hg19: chr17-5036262; COSMIC: COSV105074008;