chrY-12793060-T-C

Variant names:

• chrY-12793060-T-C
• NM_004654.4:c.3842T>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_004654.4(USP9Y):​c.3842T>C​(p.Val1281Ala) 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: 3.08
• 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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.053465337).

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.3842T>C	p.Val1281Ala	missense	Exon 27 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.3842T>C	p.Val1281Ala	missense	Exon 27 of 46	ENSP00000342812.3	O00507-1
	USP9Y	ENST00000651177.1		c.3842T>C	p.Val1281Ala	missense	Exon 29 of 48	ENSP00000498372.1	O00507-1
	USP9Y	ENST00000857541.1		c.3842T>C	p.Val1281Ala	missense	Exon 30 of 49	ENSP00000527600.1

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome Cov.: 4

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	0.077
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.81
CADD	Benign	15
DANN	Benign	0.20
DEOGEN2	Benign	0.0018	T
FATHMM_MKL	Benign	0.59	D
LIST_S2	Benign	0.73	T
M_CAP	Uncertain	0.091	D
MetaRNN	Benign	0.053	T
MutationAssessor	Benign	0.0	N
PhyloP100		3.1
PROVEAN	Benign	0.020	N
Sift	Benign	0.85	T
Sift4G	Benign	0.94	T
Polyphen		0.0	B
Vest4		0.026
MVP		0.44
MPC		0.0059
GERP RS		2.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.10
gMVP		0.25
Mutation Taster		=91/9	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-14904993;