Genetic Variant TSPYL2:p.Pro31_Pro33dup (chrX-53082576-C-CCCGCCGCCG) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_022117.4(TSPYL2):c.92_100dupCGCCGCCGC(p.Pro31_Pro33dup) variant causes a disruptive inframe insertion change. The variant allele was found at a frequency of 0.0000593 in 1,147,108 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 19 hemizygotes in GnomAD. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., 7 hem., cov: 23)

Exomes 𝑓: 0.000051 ( 0 hom. 12 hem. )

Consequence

TSPYL2
NM_022117.4 disruptive_inframe_insertion

Scores

Not classified

Clinical Significance

Not reported in ClinVar

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 -4 ACMG points.

BS2

High Hemizygotes in GnomAd4 at 7 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TSPYL2	NM_022117.4 link	c.92_100dupCGCCGCCGC	p.Pro31_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.92_100dupCGCCGCCGC	p.Pro31_Pro33dup	disruptive_inframe_insertion	Exon 1 of 7	1	NM_022117.4	ENSP00000364591.4	Q9H2G4
TSPYL2	ENST00000579390.1 link	c.92_100dupCGCCGCCGC	p.Pro31_Pro33dup	disruptive_inframe_insertion	Exon 1 of 3	5		ENSP00000462287.1	J3KS33
TSPYL2	ENST00000553557.5 link	n.224_232dupCGCCGCCGC		non_coding_transcript_exon_variant	Exon 1 of 4	2

Frequencies

GnomAD3 genomes

AF:

0.000135

AC:

AN:

110857

Hom.:

Cov.:

AF XY:

0.000210

AC XY:

AN XY:

33331

show subpopulations

Gnomad AFR

AF:

0.0000982

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000661

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000287

Gnomad SAS

AF:

0.000368

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00433

Gnomad NFE

AF:

0.0000380

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000150

AC:

AN:

66535

Hom.:

AF XY:

0.000138

AC XY:

AN XY:

21791

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000564

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000199

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000511

AC:

AN:

1036224

Hom.:

Cov.:

AF XY:

0.0000356

AC XY:

AN XY:

336810

show subpopulations

Gnomad4 AFR exome

AF:

0.0000822

Gnomad4 AMR exome

AF:

0.000552

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000164

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000258

Gnomad4 OTH exome

AF:

0.000137

GnomAD4 genome

AF:

0.000135

AC:

AN:

110884

Hom.:

Cov.:

AF XY:

0.000210

AC XY:

AN XY:

33370

show subpopulations

Gnomad4 AFR

AF:

0.0000981

Gnomad4 AMR

AF:

0.000660

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000288

Gnomad4 SAS

AF:

0.000370

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000380

Gnomad4 OTH

AF:

0.00

ClinVar

Not reported in ClinVar

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over