Y-12760490-TC-T

Position:

• chrY-12760490-TC-T

Variant summary

Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PVS1

The ENST00000338981.7(USP9Y):​c.1774del​(p.Gln592SerfsTer12) variant causes a frameshift change involving the alteration of a conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 0)
• Consequence: USP9Y ENST00000338981.7 frameshift
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.68

Genes affected

USP9Y (HGNC:12633): (ubiquitin specific peptidase 9 Y-linked) This gene is a member of the peptidase C19 family. It encodes a protein that is similar to ubiquitin-specific proteases, which cleave the ubiquitin moiety from ubiquitin-fused precursors and ubiquitinylated proteins. [provided by RefSeq, Mar 2009]

ACMG classification

Verdict is Likely_pathogenic. Variant got 8 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
USP9Y	NM_004654.4	c.1774del	p.Gln592SerfsTer12	frameshift_variant	15/46	ENST00000338981.7	NP_004645.2
USP9Y	XM_047442772.1	c.1774del	p.Gln592SerfsTer12	frameshift_variant	15/46		XP_047298728.1
USP9Y	XM_047442771.1	c.1540del	p.Gln514SerfsTer12	frameshift_variant	14/45		XP_047298727.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
USP9Y	ENST00000338981.7	c.1774del	p.Gln592SerfsTer12	frameshift_variant	15/46	1	NM_004654.4	ENSP00000342812	P1
USP9Y	ENST00000651177.1	c.1774del	p.Gln592SerfsTer12	frameshift_variant	17/48			ENSP00000498372	P1
USP9Y	ENST00000426564.6	n.1786del		non_coding_transcript_exon_variant	13/44	2

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 0

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Spermatogenic failure, Y-linked, 2 Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Juno Genomics, Hangzhou Juno Genomics, Inc

-

PVS1_Supporting+PM2_Supporting+PP4 -

Computational scores

Source: dbNSFP v4.3

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrY-14872420;