Y-12786501-CTT-C

Position:

• chrY-12786501-CTT-C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP6_Moderate BS2

The NM_004654.4(USP9Y):​c.3283-6_3283-5del variant causes a 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 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.988

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

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• 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 id is 3049353.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Hemizygotes in GnomAd4 at 3 YL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
USP9Y	NM_004654.4	c.3283-6_3283-5del		intron_variant		ENST00000338981.7
USP9Y	XM_047442771.1	c.3049-6_3049-5del		intron_variant
USP9Y	XM_047442772.1	c.3283-6_3283-5del		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
USP9Y	ENST00000338981.7	c.3283-6_3283-5del		intron_variant		1	NM_004654.4	P1
USP9Y	ENST00000651177.1	c.3283-6_3283-5del		intron_variant				P1
USP9Y	ENST00000426564.6	n.3295-6_3295-5del		intron_variant, non_coding_transcript_variant		2

Frequencies

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

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

Gnomad4 AFR exome AF: 0.000283

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

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

Gnomad4 AFR AF: 0.000714

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

USP9Y-related disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Aug 09, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs149106583; hg19: chrY-14898435;