chrY-12840450-C-T

Variant names:

• chrY-12840450-C-T
• NM_004654.4:c.5924C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_004654.4(USP9Y):​c.5924C>T​(p.Thr1975Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 11/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 0)
• Consequence: USP9Y NM_004654.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.51
• 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.07187161).

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.5924C>T	p.Thr1975Ile	missense	Exon 36 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.5924C>T	p.Thr1975Ile	missense	Exon 36 of 46	ENSP00000342812.3	O00507-1
	USP9Y	ENST00000651177.1		c.5924C>T	p.Thr1975Ile	missense	Exon 38 of 48	ENSP00000498372.1	O00507-1
	USP9Y	ENST00000857541.1		c.5924C>T	p.Thr1975Ile	missense	Exon 39 of 49	ENSP00000527600.1

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome Cov.: 1

GnomAD4 genome Cov.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	-0.50	T
BayesDel_noAF	Benign	-0.95
CADD	Benign	18
DANN	Benign	0.85
DEOGEN2	Benign	0.024	T
FATHMM_MKL	Benign	0.19	N
LIST_S2	Benign	0.85	T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.072	T
MutationAssessor	Benign	1.6	L
PhyloP100		3.5
PROVEAN	Benign	-2.1	N
Sift	Uncertain	0.011	D
Sift4G	Uncertain	0.039	D
Polyphen		0.0070	B
Vest4		0.084
MVP		0.20
MPC		0.0063
GERP RS		1.4
Varity_R		0.13
gMVP		0.76
Mutation Taster		=65/35	polymorphism

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

hg19: chrY-14952376;