dbSNP rs756258319: USP9Y:p.Val2077Ile (chrY-12842256-G-A) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_ModerateBP6_ModerateBS2

The NM_004654.4(USP9Y):c.6229G>A(p.Val2077Ile) variant causes a missense change. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00060 ( 0 hom., 20 hem., cov: 0)

Exomes 𝑓: 0.000041 ( 0 hom. 15 hem. )

Consequence

USP9Y
NM_004654.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.00

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.12544295).

BP6

Variant Y-12842256-G-A is Benign according to our data. Variant chrY-12842256-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3467348.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAd4 at 20 YL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
USP9Y	NM_004654.4 link	c.6229G>A	p.Val2077Ile	missense_variant	Exon 38 of 46	ENST00000338981.7	NP_004645.2	O00507-1
USP9Y	XM_047442772.1 link	c.6229G>A	p.Val2077Ile	missense_variant	Exon 38 of 46		XP_047298728.1
USP9Y	XM_047442771.1 link	c.5995G>A	p.Val1999Ile	missense_variant	Exon 37 of 45		XP_047298727.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
USP9Y	ENST00000338981.7 link	c.6229G>A	p.Val2077Ile	missense_variant	Exon 38 of 46	1	NM_004654.4	ENSP00000342812.3	O00507-1
USP9Y	ENST00000651177.1 link	c.6229G>A	p.Val2077Ile	missense_variant	Exon 40 of 48			ENSP00000498372.1	O00507-1
USP9Y	ENST00000426564.6 link	n.6256G>A		non_coding_transcript_exon_variant	Exon 36 of 44	2

Frequencies

GnomAD3 genomes

AF:

0.000604

AC:

AN:

33129

Hom.:

Cov.:

AF XY:

0.000604

AC XY:

AN XY:

33129

show subpopulations

Gnomad AFR

AF:

0.000234

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00508

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

GnomAD3 exomes

AF:

0.000192

AC:

AN:

67546

Hom.:

AF XY:

0.000192

AC XY:

AN XY:

67546

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00168

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000629

GnomAD4 exome

AF:

0.0000414

AC:

AN:

362654

Hom.:

Cov.:

AF XY:

0.0000414

AC XY:

AN XY:

362654

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00137

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000105

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000372

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.000604

AC:

AN:

33129

Hom.:

Cov.:

AF XY:

0.000604

AC XY:

AN XY:

33129

show subpopulations

Gnomad4 AFR

AF:

0.000234

Gnomad4 AMR

AF:

0.00508

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

ExAC

AF:

0.0000279

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Nov 13, 2024

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.055

BayesDel_addAF

Benign

-0.83

BayesDel_noAF

Benign

-0.99

CADD

Benign

DANN

Benign

0.28

DEOGEN2

Benign

0.0043

FATHMM_MKL

Benign

0.16

LIST_S2

Benign

0.57

M_CAP

Pathogenic

0.42

MetaRNN

Benign

0.13

MutationAssessor

Benign

-0.56

PROVEAN

Benign

-0.13

Sift

Benign

0.58

Sift4G

Benign

0.41

Polyphen

0.0010

Vest4

0.17

MVP

0.15

MPC

0.0067

GERP RS

1.1

Varity_R

0.089

gMVP

0.052

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

Details are displayed if max score is > 0.2

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