rs34601266

Variant names:

• chrY-12778040-C-T
• rs34601266
• NM_004654.4:c.2661C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_004654.4(USP9Y):​c.2661C>T​(p.Leu887Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0015 (0 hom., 50 hem., cov: 0)
  • Exomes 𝑓: 0.0018 (0 hom. 664 hem.)
• Consequence: USP9Y NM_004654.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.439
• Publications: 2 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: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP6: Variant Y-12778040-C-T is Benign according to our data. Variant chrY-12778040-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2661886.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.439 with no splicing effect.
• BS2: High Hemizygotes in GnomAd4 at 50 YL gene

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.2661C>T	p.Leu887Leu	synonymous	Exon 20 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.2661C>T	p.Leu887Leu	synonymous	Exon 20 of 46	ENSP00000342812.3	O00507-1
	USP9Y	ENST00000651177.1		c.2661C>T	p.Leu887Leu	synonymous	Exon 22 of 48	ENSP00000498372.1	O00507-1
	USP9Y	ENST00000857541.1		c.2661C>T	p.Leu887Leu	synonymous	Exon 23 of 49	ENSP00000527600.1

Frequencies

GnomAD3 genomes AF: 0.00151 AC: 49 AN: 32461 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000574

Gnomad ASJ AF: 0.0302

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00141

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00128

Gnomad OTH AF: 0.00708

GnomAD2 exomes AF: 0.00334 AC: 217 AN: 64901 AF XY: 0.00334

Gnomad AFR exome AF: 0.000336

Gnomad AMR exome AF: 0.00144

Gnomad ASJ exome AF: 0.0523

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00156

Gnomad OTH exome AF: 0.00392

GnomAD4 exome AF: 0.00184 AC: 664 AN: 360895 Hom.: 0 Cov.: 0 AF XY: 0.00184 AC XY: 664 AN XY: 360895

African (AFR) AF: 0.00 AC: 0 AN: 7039

American (AMR) AF: 0.00191 AC: 18 AN: 9406

Ashkenazi Jewish (ASJ) AF: 0.0447 AC: 299 AN: 6693

East Asian (EAS) AF: 0.00 AC: 0 AN: 9413

South Asian (SAS) AF: 0.00247 AC: 78 AN: 31623

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 12752

Middle Eastern (MID) AF: 0.00802 AC: 13 AN: 1620

European-Non Finnish (NFE) AF: 0.000638 AC: 171 AN: 268169

Other (OTH) AF: 0.00599 AC: 85 AN: 14180

GnomAD4 genome AF: 0.00154 AC: 50 AN: 32522 Hom.: 0 Cov.: 0 AF XY: 0.00154 AC XY: 50 AN XY: 32522

African (AFR) AF: 0.000240 AC: 2 AN: 8332

American (AMR) AF: 0.000573 AC: 2 AN: 3490

Ashkenazi Jewish (ASJ) AF: 0.0302 AC: 23 AN: 762

East Asian (EAS) AF: 0.00 AC: 0 AN: 1293

South Asian (SAS) AF: 0.00211 AC: 3 AN: 1422

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 3202

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 71

European-Non Finnish (NFE) AF: 0.00128 AC: 17 AN: 13312

Other (OTH) AF: 0.00703 AC: 3 AN: 427

Alfa AF: 0.00522 Hom.: 63

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	2.6
DANN	Benign	0.44
PhyloP100		0.44

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs34601266; hg19: chrY-14889974;