Genetic Variant USP9Y:p.Met134Thr (chrY-12725188-T-C) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_004654.4(USP9Y):c.401T>C(p.Met134Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 10/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

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

Exomes 𝑓: 0.0000083 ( 0 hom. 3 hem. )

Failed GnomAD Quality Control

Consequence

USP9Y
NM_004654.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.97

Publications

0 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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.05739689).

BP6

Variant Y-12725188-T-C is Benign according to our data. Variant chrY-12725188-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 3467347.Status of the report is criteria_provided_single_submitter, 1 stars.

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.401T>C	p.Met134Thr	missense	Exon 6 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.401T>C	p.Met134Thr	missense	Exon 6 of 46	ENSP00000342812.3	O00507-1
USP9Y	ENST00000651177.1		c.401T>C	p.Met134Thr	missense	Exon 8 of 48	ENSP00000498372.1	O00507-1
USP9Y	ENST00000857541.1		c.401T>C	p.Met134Thr	missense	Exon 9 of 49	ENSP00000527600.1

Frequencies

GnomAD3 genomes

AF:

0.0000297

AC:

AN:

33650

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000279

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

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000829

AC:

AN:

361843

Hom.:

Cov.:

AF XY:

0.00000829

AC XY:

AN XY:

361843

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

7050

American (AMR)

AF:

0.000210

AC:

AN:

9504

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

6712

East Asian (EAS)

AF:

0.00

AC:

AN:

9439

South Asian (SAS)

AF:

0.00

AC:

AN:

32039

European-Finnish (FIN)

AF:

0.00

AC:

AN:

12840

Middle Eastern (MID)

AF:

0.000620

AC:

AN:

1612

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

268412

Other (OTH)

AF:

0.00

AC:

AN:

14235

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:

0.0000297

AC:

AN:

33650

Hom.:

Cov.:

AF XY:

0.0000297

AC XY:

AN XY:

33650

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

8683

American (AMR)

AF:

0.000279

AC:

AN:

3583

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

774

East Asian (EAS)

AF:

0.00

AC:

AN:

1326

South Asian (SAS)

AF:

0.00

AC:

AN:

1498

European-Finnish (FIN)

AF:

0.00

AC:

AN:

3446

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

13584

Other (OTH)

AF:

0.00

AC:

AN:

466

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-1.0

CADD

Benign

5.2

(source)

DANN

Benign

0.20

DEOGEN2

Benign

0.00081

FATHMM_MKL

Benign

0.062

LIST_S2

Benign

0.49

M_CAP

Uncertain

0.21

MetaRNN

Benign

0.057

MutationAssessor

Benign

-1.9

PhyloP100

2.0

PROVEAN

Benign

3.7

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.27

MVP

0.15

MPC

0.0060

GERP RS

0.61

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.056

gMVP

0.66

Mutation Taster

=94/6

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over