Y-12786501-CTTTTT-CTTT

Variant names:

• chrY-12786501-CTT-C
• rs149106583
• NM_004654.4:c.3283-6_3283-5delTT

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_004654.4(USP9Y):​c.3283-6_3283-5delTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000156 in 257,230 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00016 (0 hom., 3 hem., cov: 0)
  • Exomes 𝑓: 0.0000042 (0 hom. 1 hem.)
• Consequence: USP9Y NM_004654.4 splice_region, intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.988
• 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 -6 ACMG points.

• BP6: Variant Y-12786501-CTT-C is Benign according to our data. Variant chrY-12786501-CTT-C is described in ClinVar as Likely_benign. ClinVar VariationId is 3049353.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Hemizygotes in GnomAd4 at 3 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.3283-6_3283-5delTT		splice_region intron	N/A	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.3283-20_3283-19delTT		intron	N/A	ENSP00000342812.3	O00507-1
	USP9Y	ENST00000651177.1		c.3283-20_3283-19delTT		intron	N/A	ENSP00000498372.1	O00507-1
	USP9Y	ENST00000857541.1		c.3283-20_3283-19delTT		intron	N/A	ENSP00000527600.1

Frequencies

GnomAD3 genomes AF: 0.000164 AC: 3 AN: 18345 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000717

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000419 AC: 1 AN: 238886 Hom.: 0 AF XY: 0.00000419 AC XY: 1 AN XY: 238886

African (AFR) AF: 0.000283 AC: 1 AN: 3533

American (AMR) AF: 0.00 AC: 0 AN: 5964

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3642

East Asian (EAS) AF: 0.00 AC: 0 AN: 4150

South Asian (SAS) AF: 0.00 AC: 0 AN: 20639

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5224

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 701

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 185928

Other (OTH) AF: 0.00 AC: 0 AN: 9105

GnomAD4 genome AF: 0.000164 AC: 3 AN: 18344 Hom.: 0 Cov.: 0 AF XY: 0.000164 AC XY: 3 AN XY: 18344

African (AFR) AF: 0.000714 AC: 3 AN: 4201

American (AMR) AF: 0.00 AC: 0 AN: 2133

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 449

East Asian (EAS) AF: 0.00 AC: 0 AN: 619

South Asian (SAS) AF: 0.00 AC: 0 AN: 837

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 821

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 34

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 8841

Other (OTH) AF: 0.00 AC: 0 AN: 242

Alfa AF: 0.0138 Hom.: 57

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	USP9Y-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.99

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs149106583; hg19: chrY-14898435;