Variant Y-12735724-TTAAG-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PP3_ModeratePP5

The NM_004654.4(USP9Y):c.773+3_773+6del variant causes a splice donor, coding sequence change involving the alteration of a conserved nucleotide. 1/1 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: 𝑓 0.000030 ( 0 hom., 1 hem., cov: 0)

Exomes 𝑓: 0.000026 ( 0 hom. 8 hem. )

Failed GnomAD Quality Control

Consequence

USP9Y
NM_004654.4 splice_donor, coding_sequence

Scores

Not classified

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 8.69

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 Pathogenic. Variant got 11 ACMG points.

PVS1

Splicing +-2 bp (donor or acceptor) variant, LoF is a know mechanism of disease, No cryptic splice site detected. Exon removal results in frameshift change.

PP3

Splicing scoreres supports a deletorius effect: Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.

PP5

Variant Y-12735724-TTAAG-T is Pathogenic according to our data. Variant chrY-12735724-TTAAG-T is described in ClinVar as [Pathogenic]. Clinvar id is 9757.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chrY-12735724-TTAAG-T is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE
USP9Y	NM_004654.4 linkuse as main transcript	c.773+3_773+6del	splice_donor_variant, coding_sequence_variant	8/46	ENST00000338981.7
USP9Y	XM_047442771.1 linkuse as main transcript	c.539+3_539+6del	splice_donor_variant, coding_sequence_variant	7/45
USP9Y	XM_047442772.1 linkuse as main transcript	c.773+3_773+6del	splice_donor_variant, coding_sequence_variant	8/46

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Appris	UniProt
USP9Y	ENST00000338981.7 linkuse as main transcript	c.773+3_773+6del	splice_donor_variant, coding_sequence_variant	8/46	1	NM_004654.4	P1	O00507-1
USP9Y	ENST00000651177.1 linkuse as main transcript	c.773+3_773+6del	splice_donor_variant, coding_sequence_variant	10/48			P1	O00507-1
USP9Y	ENST00000426564.6 linkuse as main transcript	n.785+3_785+6del	splice_donor_variant, non_coding_transcript_exon_variant	6/44	2

Frequencies

GnomAD3 genomes

AF:

0.0000299

AC:

AN:

33426

Hom.:

Cov.:

AF XY:

0.0000299

AC XY:

AN XY:

33426

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000742

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000174

AC:

AN:

57348

Hom.:

AF XY:

0.0000174

AC XY:

AN XY:

57348

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000103

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000263

AC:

AN:

303969

Hom.:

AF XY:

0.0000263

AC XY:

AN XY:

303969

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.000158

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000337

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000276

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000299

AC:

AN:

33426

Hom.:

Cov.:

AF XY:

0.0000299

AC XY:

AN XY:

33426

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.0000742

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Spermatogenic failure, Y-linked, 2

Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Dec 01, 1999

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

1.0

Details are displayed if max score is > 0.2

DS_DL_spliceai

1.0

Position offset: 3

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