Variant rs3212292 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -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. The variant allele was found at a frequency of 0.000148 in 33,894 control chromosomes in the GnomAD database, with no homozygous occurrence. 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

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 Likely_benign. Variant got -3 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.807

BS2

High Hemizygotes in GnomAd at 5 YL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
USP9Y	NM_004654.4 linkuse as main transcript	c.1397T>A	p.Leu466His	missense_variant	12/46	ENST00000338981.7
USP9Y	XM_047442772.1 linkuse as main transcript	c.1397T>A	p.Leu466His	missense_variant	12/46
USP9Y	XM_047442771.1 linkuse as main transcript	c.1163T>A	p.Leu388His	missense_variant	11/45

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
USP9Y	ENST00000338981.7 linkuse as main transcript	c.1397T>A	p.Leu466His	missense_variant	12/46	1	NM_004654.4	P1	O00507-1
USP9Y	ENST00000651177.1 linkuse as main transcript	c.1397T>A	p.Leu466His	missense_variant	14/48			P1	O00507-1
USP9Y	ENST00000426564.6 linkuse as main transcript	n.1409T>A		non_coding_transcript_exon_variant	10/44	2

Frequencies

GnomAD3 genomes

AF:

0.000148

AC:

AN:

33833

Hom.:

Cov.:

AF XY:

0.000148

AC XY:

AN XY:

33833

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

GnomAD3 exomes

AF:

0.0000742

AC:

AN:

67394

Hom.:

AF XY:

0.0000742

AC XY:

AN XY:

67394

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 SAS exome

AF:

0.00

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

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000746

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.000148

AC:

AN:

33894

Hom.:

Cov.:

AF XY:

0.000148

AC XY:

AN XY:

33894

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00381

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

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

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

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

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over