NM_004654.4:c.6343G>T

Variant names:

• chrY-12842370-G-T
• rs1286380745
• NM_004654.4:c.6343G>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_004654.4(USP9Y):​c.6343G>T​(p.Gly2115Cys) variant causes a missense change involving the alteration of a conserved nucleotide. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: not found (cov: 0)
• Consequence: USP9Y NM_004654.4 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 9.43
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.833

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004654.4. 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
	USP9Y	NM_004654.4	MANE Select	c.6343G>T	p.Gly2115Cys	missense	Exon 38 of 46	NP_004645.2	O00507-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USP9Y	ENST00000338981.7	TSL:1 MANE Select	c.6343G>T	p.Gly2115Cys	missense	Exon 38 of 46	ENSP00000342812.3	O00507-1
	USP9Y	ENST00000651177.1		c.6343G>T	p.Gly2115Cys	missense	Exon 40 of 48	ENSP00000498372.1	O00507-1
	USP9Y	ENST00000857541.1		c.6343G>T	p.Gly2115Cys	missense	Exon 41 of 49	ENSP00000527600.1

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	1	-	Spermatogenic failure, Y-linked, 2 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Uncertain	0.015	T
BayesDel_noAF	Benign	-0.22
CADD	Pathogenic	29
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0072	T
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Uncertain	0.27	D
MetaRNN	Pathogenic	0.83	D
MutationAssessor	Benign	1.6	L
PhyloP100		9.4
PROVEAN	Benign	-1.5	N
Sift	Benign	0.043	D
Sift4G	Benign	0.090	T
Polyphen		0.97	D
Vest4		0.73
MVP		0.79
MPC		0.021
GERP RS		2.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.43
gMVP		0.50
Mutation Taster		=39/61	disease causing

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

Other links and lift over

dbSNP: rs1286380745; hg19: chrY-14954296;