Genetic Variant USP9Y:c.3283-6_3283-5delTT (chrY-12786501-CTT-C) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP6_ModerateBS2

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

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.988

Variant links:

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]

USP9Y links:

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ACMG classification

Classification made for transcript

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	Effect	Exon rank	MANE	Protein	UniProt
USP9Y	NM_004654.4 link	c.3283-6_3283-5delTT	splice_region_variant, intron_variant	Intron 23 of 45	ENST00000338981.7	NP_004645.2	O00507-1
USP9Y	XM_047442772.1 link	c.3283-6_3283-5delTT	splice_region_variant, intron_variant	Intron 23 of 45		XP_047298728.1
USP9Y	XM_047442771.1 link	c.3049-6_3049-5delTT	splice_region_variant, intron_variant	Intron 22 of 44		XP_047298727.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
USP9Y	ENST00000338981.7 link	c.3283-20_3283-19delTT	intron_variant	Intron 23 of 45	1	NM_004654.4	ENSP00000342812.3	O00507-1
USP9Y	ENST00000651177.1 link	c.3283-20_3283-19delTT	intron_variant	Intron 25 of 47			ENSP00000498372.1	O00507-1
USP9Y	ENST00000426564.6 link	n.3295-20_3295-19delTT	intron_variant	Intron 21 of 43	2

Frequencies

GnomAD3 genomes

AF:

0.000164

AC:

AN:

18345

Hom.:

Cov.:

AF XY:

0.000164

AC XY:

AN XY:

18345

show subpopulations

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:

AN:

238886

Hom.:

AF XY:

0.00000419

AC XY:

AN XY:

238886

show subpopulations

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:

AN:

18344

Hom.:

Cov.:

AF XY:

0.000164

AC XY:

AN XY:

18344

show subpopulations

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

LINK: link

Submissions by phenotype

USP9Y-related disorder

Benign:1

Aug 09, 2019

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

Name

Calibrated prediction

Score

Prediction

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over