dbSNP rs3212292: USP9Y:p.Leu466His (chrY-12739604-T-A) – ACMG Classification: Likely_benign (-3 pts)

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 1P and 4B. PP3BS2

The NM_004654.4(USP9Y):c.1397T>A(p.Leu466His) variant causes a missense change involving the alteration of a conserved nucleotide. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00015 ( 0 hom., 5 hem., cov: 0)

Exomes 𝑓: 0.000020 ( 0 hom. 7 hem. )

Failed GnomAD Quality Control

Consequence

USP9Y
NM_004654.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.52

Publications

4 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -3 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.807

BS2

High Hemizygotes in GnomAd4 at 5 YL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
USP9Y	NM_004654.4 link	c.1397T>A	p.Leu466His	missense_variant	Exon 12 of 46	ENST00000338981.7	NP_004645.2	O00507-1
USP9Y	XM_047442772.1 link	c.1397T>A	p.Leu466His	missense_variant	Exon 12 of 46		XP_047298728.1
USP9Y	XM_047442771.1 link	c.1163T>A	p.Leu388His	missense_variant	Exon 11 of 45		XP_047298727.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
USP9Y	ENST00000338981.7 link	c.1397T>A	p.Leu466His	missense_variant	Exon 12 of 46	1	NM_004654.4	ENSP00000342812.3	O00507-1
USP9Y	ENST00000651177.1 link	c.1397T>A	p.Leu466His	missense_variant	Exon 14 of 48			ENSP00000498372.1	O00507-1
USP9Y	ENST00000426564.6 link	n.1409T>A		non_coding_transcript_exon_variant	Exon 10 of 44	2

Frequencies

GnomAD3 genomes

AF:

0.000148

AC:

AN:

33833

Hom.:

Cov.:

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:

0.00381

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

GnomAD2 exomes

AF:

0.0000742

AC:

AN:

67394

AF XY:

0.0000742

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00111

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:

0.0000195

AC:

AN:

358464

Hom.:

Cov.:

AF XY:

0.0000195

AC XY:

AN XY:

358464

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

6995

American (AMR)

AF:

0.00

AC:

AN:

9464

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

6669

East Asian (EAS)

AF:

0.000746

AC:

AN:

9382

South Asian (SAS)

AF:

0.00

AC:

AN:

31812

European-Finnish (FIN)

AF:

0.00

AC:

AN:

12759

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1613

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

265669

Other (OTH)

AF:

0.00

AC:

AN:

14101

GnomAD4 genome

AF:

0.000148

AC:

AN:

33894

Hom.:

Cov.:

AF XY:

0.000148

AC XY:

AN XY:

33894

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

8817

American (AMR)

AF:

0.00

AC:

AN:

3635

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

774

East Asian (EAS)

AF:

0.00381

AC:

AN:

1313

South Asian (SAS)

AF:

0.00

AC:

AN:

1555

European-Finnish (FIN)

AF:

0.00

AC:

AN:

3424

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

13604

Other (OTH)

AF:

0.00

AC:

AN:

485

ExAC

AF:

0.0000285

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.89

BayesDel_addAF

Benign

-0.041

BayesDel_noAF

Uncertain

0.12

CADD

Pathogenic

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.20

FATHMM_MKL

Uncertain

0.92

LIST_S2

Pathogenic

0.97

M_CAP

Pathogenic

0.34

MetaRNN

Pathogenic

0.81

MutationAssessor

Uncertain

2.7

PhyloP100

7.5

PROVEAN

Pathogenic

-5.9

Sift

Uncertain

0.0010

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.87

MVP

0.81

MPC

0.026

GERP RS

2.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.72

gMVP

0.79

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

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rs3212292

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over