Genetic Variant NM_004654.4:c.401T>C (chrY-12725188-T-C) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. Variant got -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. 10/17 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

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 Likely_benign. Variant got -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 id is 3467347.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
USP9Y	NM_004654.4 link	c.401T>C	p.Met134Thr	missense_variant	Exon 6 of 46	ENST00000338981.7	NP_004645.2	O00507-1
USP9Y	XM_047442772.1 link	c.401T>C	p.Met134Thr	missense_variant	Exon 6 of 46		XP_047298728.1
USP9Y	XM_047442771.1 link	c.167T>C	p.Met56Thr	missense_variant	Exon 5 of 45		XP_047298727.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
USP9Y	ENST00000338981.7 link	c.401T>C	p.Met134Thr	missense_variant	Exon 6 of 46	1	NM_004654.4	ENSP00000342812.3	O00507-1
USP9Y	ENST00000651177.1 link	c.401T>C	p.Met134Thr	missense_variant	Exon 8 of 48			ENSP00000498372.1	O00507-1
USP9Y	ENST00000426564.6 link	n.413T>C		non_coding_transcript_exon_variant	Exon 4 of 44	2

Frequencies

GnomAD3 genomes

AF:

0.0000297

AC:

AN:

33650

Hom.:

Cov.:

AF XY:

0.0000297

AC XY:

AN XY:

33650

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

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000210

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

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:

0.0000297

AC:

AN:

33650

Hom.:

Cov.:

AF XY:

0.0000297

AC XY:

AN XY:

33650

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000279

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

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Dec 10, 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

0.066

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-1.0

CADD

Benign

5.2

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

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

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

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