Genetic Variant NM_022117.4:c.98_100dupCGC (chrX-53082576-C-CCCG) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP6_ModerateBS2

The NM_022117.4(TSPYL2):c.98_100dupCGC(p.Pro33dup) variant causes a disruptive inframe insertion change. The variant allele was found at a frequency of 0.00107 in 1,146,769 control chromosomes in the GnomAD database, including 4 homozygotes. There are 208 hemizygotes in GnomAD. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00099 ( 0 hom., 35 hem., cov: 23)

Exomes 𝑓: 0.0011 ( 4 hom. 173 hem. )

Consequence

TSPYL2
NM_022117.4 disruptive_inframe_insertion

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.25

Publications

2 publications found

Variant links:

Genes affected

TSPYL2 (HGNC:24358): (TSPY like 2) This gene encodes a member of the testis-specific protein Y-encoded, TSPY-like/SET/nucleosome assembly protein-1 superfamily. The encoded protein is localized to the nucleolus where it functions in chromatin remodeling and as an inhibitor of cell-cycle progression. This protein may play a role in the suppression of tumor growth. [provided by RefSeq, Sep 2009]

TSPYL2 links:

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ACMG classification

Classification was made for transcript

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

BP6

Variant X-53082576-C-CCCG is Benign according to our data. Variant chrX-53082576-C-CCCG is described in ClinVar as Likely_benign. ClinVar VariationId is 252735.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAd4 at 35 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022117.4. 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
	TSPYL2	NM_022117.4	MANE Select	c.98_100dupCGC	p.Pro33dup	disruptive_inframe_insertion	Exon 1 of 7	NP_071400.1	Q9H2G4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TSPYL2	ENST00000375442.8	TSL:1 MANE Select	c.98_100dupCGC	p.Pro33dup	disruptive_inframe_insertion	Exon 1 of 7	ENSP00000364591.4	Q9H2G4
TSPYL2	ENST00000912653.1		c.98_100dupCGC	p.Pro33dup	disruptive_inframe_insertion	Exon 1 of 7	ENSP00000582712.1
TSPYL2	ENST00000887608.1		c.98_100dupCGC	p.Pro33dup	disruptive_inframe_insertion	Exon 1 of 7	ENSP00000557667.1

Frequencies

GnomAD3 genomes

AF:

0.000992

AC:

110

AN:

110858

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000688

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000850

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00660

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00106

Gnomad OTH

AF:

0.000670

GnomAD2 exomes

AF:

0.000676

AC:

AN:

66535

AF XY:

0.000275

show subpopulations

Gnomad AFR exome

AF:

0.000376

Gnomad AMR exome

AF:

0.000211

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00342

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000753

Gnomad OTH exome

AF:

0.000480

GnomAD4 exome

AF:

0.00108

AC:

1120

AN:

1035884

Hom.:

Cov.:

AF XY:

0.000514

AC XY:

173

AN XY:

336462

show subpopulations

African (AFR)

AF:

0.000452

AC:

AN:

24316

American (AMR)

AF:

0.000258

AC:

AN:

27161

Ashkenazi Jewish (ASJ)

AF:

0.0000549

AC:

AN:

18225

East Asian (EAS)

AF:

0.0154

AC:

412

AN:

26723

South Asian (SAS)

AF:

0.000389

AC:

AN:

48891

European-Finnish (FIN)

AF:

0.00

AC:

AN:

28704

Middle Eastern (MID)

AF:

0.000328

AC:

AN:

3052

European-Non Finnish (NFE)

AF:

0.000777

AC:

633

AN:

815014

Other (OTH)

AF:

0.000822

AC:

AN:

43798

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.460

Heterozygous variant carriers

114

171

228

285

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

150

<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:

0.000992

AC:

110

AN:

110885

Hom.:

Cov.:

AF XY:

0.00105

AC XY:

AN XY:

33371

show subpopulations

African (AFR)

AF:

0.000686

AC:

AN:

30591

American (AMR)

AF:

0.000849

AC:

AN:

10605

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2637

East Asian (EAS)

AF:

0.00663

AC:

AN:

3469

South Asian (SAS)

AF:

0.00

AC:

AN:

2704

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5857

Middle Eastern (MID)

AF:

0.00

AC:

AN:

209

European-Non Finnish (NFE)

AF:

0.00106

AC:

AN:

52630

Other (OTH)

AF:

0.000661

AC:

AN:

1512

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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:

0.000475

Hom.:

Bravo

AF:

0.000914

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

PhyloP100

4.3

Mutation Taster

=88/12

polymorphism

(source)

Splicing

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

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