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

new If you want to explore the variant's impact on the transcript NM_004654.4, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004654.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USP9Y	NM_004654.4	MANE Select	c.1397T>A	p.Leu466His	missense	Exon 12 of 46	NP_004645.2	O00507-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
USP9Y	ENST00000338981.7	TSL:1 MANE Select	c.1397T>A	p.Leu466His	missense	Exon 12 of 46	ENSP00000342812.3	O00507-1
USP9Y	ENST00000651177.1		c.1397T>A	p.Leu466His	missense	Exon 14 of 48	ENSP00000498372.1	O00507-1
USP9Y	ENST00000857541.1		c.1397T>A	p.Leu466His	missense	Exon 15 of 49	ENSP00000527600.1

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

Age Distribution

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

Age Distribution

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over