Genetic Variant NM_004654.4:c.4491C>T (chrY-12812934-C-T) – ACMG Classification: Benign (-15 pts)

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_004654.4(USP9Y):c.4491C>T(p.Pro1497Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0023 ( 0 hom., 77 hem., cov: 0)

Exomes 𝑓: 0.0015 ( 0 hom. 558 hem. )

Consequence

USP9Y
NM_004654.4 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.907

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: Benign. The variant received -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.5).

BP6

Variant Y-12812934-C-T is Benign according to our data. Variant chrY-12812934-C-T is described in ClinVar as Benign. ClinVar VariationId is 1269192.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.907 with no splicing effect.

BS1

Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.00229 (77/33692) while in subpopulation EAS AF = 0.0579 (75/1296). AF 95% confidence interval is 0.0473. There are 0 homozygotes in GnomAd4. There are 77 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.

BS2

High Hemizygotes in GnomAd4 at 77 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.4491C>T	p.Pro1497Pro	synonymous	Exon 31 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.4491C>T	p.Pro1497Pro	synonymous	Exon 31 of 46	ENSP00000342812.3	O00507-1
USP9Y	ENST00000651177.1		c.4491C>T	p.Pro1497Pro	synonymous	Exon 33 of 48	ENSP00000498372.1	O00507-1
USP9Y	ENST00000857541.1		c.4491C>T	p.Pro1497Pro	synonymous	Exon 34 of 49	ENSP00000527600.1

Frequencies

GnomAD3 genomes

AF:

0.00229

AC:

AN:

33630

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:

0.0578

Gnomad SAS

AF:

0.000651

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00211

GnomAD2 exomes

AF:

0.00482

AC:

327

AN:

67885

AF XY:

0.00482

show subpopulations

Gnomad AFR exome

AF:

0.000323

Gnomad AMR exome

AF:

0.000559

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0696

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00187

GnomAD4 exome

AF:

0.00154

AC:

558

AN:

362757

Hom.:

Cov.:

AF XY:

0.00154

AC XY:

558

AN XY:

362757

show subpopulations

African (AFR)

AF:

0.000142

AC:

AN:

7061

American (AMR)

AF:

0.000631

AC:

AN:

9514

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

6738

East Asian (EAS)

AF:

0.0520

AC:

493

AN:

9478

South Asian (SAS)

AF:

0.000561

AC:

AN:

32093

European-Finnish (FIN)

AF:

0.00

AC:

AN:

12881

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1629

European-Non Finnish (NFE)

AF:

0.00000372

AC:

AN:

269088

Other (OTH)

AF:

0.00273

AC:

AN:

14275

Age Distribution

Exome Hom

Variant carriers

100

<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:

0.00229

AC:

AN:

33692

Hom.:

Cov.:

AF XY:

0.00229

AC XY:

AN XY:

33692

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

8637

American (AMR)

AF:

0.00

AC:

AN:

3735

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

766

East Asian (EAS)

AF:

0.0579

AC:

AN:

1296

South Asian (SAS)

AF:

0.000650

AC:

AN:

1538

European-Finnish (FIN)

AF:

0.00

AC:

AN:

3339

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

13617

Other (OTH)

AF:

0.00210

AC:

AN:

477

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

Alfa

AF:

0.0436

Hom.:

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.50

CADD

Benign

1.9

(source)

DANN

Benign

0.36

PhyloP100

0.91

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

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over