Genetic Variant TSPYL2:p.Pro33dup (chrX-53082576-C-CCCG) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. Variant got -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

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 made for transcript

Verdict is Likely_benign. Variant got -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 id is 252735.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAd4 at 35 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TSPYL2	NM_022117.4 link	c.98_100dupCGC	p.Pro33dup	disruptive_inframe_insertion	Exon 1 of 7	ENST00000375442.8	NP_071400.1	Q9H2G4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
TSPYL2	ENST00000375442.8 link	c.98_100dupCGC	p.Pro33dup	disruptive_inframe_insertion	Exon 1 of 7	1	NM_022117.4	ENSP00000364591.4	Q9H2G4
TSPYL2	ENST00000579390.1 link	c.98_100dupCGC	p.Pro33dup	disruptive_inframe_insertion	Exon 1 of 3	5		ENSP00000462287.1	J3KS33
TSPYL2	ENST00000553557.5 link	n.230_232dupCGC		non_coding_transcript_exon_variant	Exon 1 of 4	2

Frequencies

GnomAD3 genomes

AF:

0.000992

AC:

110

AN:

110858

Hom.:

Cov.:

AF XY:

0.00105

AC XY:

AN XY:

33332

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

GnomAD3 exomes

AF:

0.000676

AC:

AN:

66535

Hom.:

AF XY:

0.000275

AC XY:

AN XY:

21791

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 SAS exome

AF:

0.000497

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

Gnomad4 AFR exome

AF:

0.000452

Gnomad4 AMR exome

AF:

0.000258

Gnomad4 ASJ exome

AF:

0.0000549

Gnomad4 EAS exome

AF:

0.0154

Gnomad4 SAS exome

AF:

0.000389

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000777

Gnomad4 OTH exome

AF:

0.000822

GnomAD4 genome

AF:

0.000992

AC:

110

AN:

110885

Hom.:

Cov.:

AF XY:

0.00105

AC XY:

AN XY:

33371

show subpopulations

Gnomad4 AFR

AF:

0.000686

Gnomad4 AMR

AF:

0.000849

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00663

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00106

Gnomad4 OTH

AF:

0.000661

Bravo

AF:

0.000914

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Nov 06, 2015

Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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