Genetic Variant TSPYL2:p.Pro32_Pro33del (chrX-53082576-CCCGCCG-C) – 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.95_100delCGCCGC(p.Pro32_Pro33del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.000894 in 1,146,989 control chromosomes in the GnomAD database, including 1 homozygotes. There are 284 hemizygotes in GnomAD. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00074 ( 1 hom., 22 hem., cov: 23)

Exomes 𝑓: 0.00091 ( 0 hom. 262 hem. )

Consequence

TSPYL2
NM_022117.4 disruptive_inframe_deletion

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP6

Variant X-53082576-CCCGCCG-C is Benign according to our data. Variant chrX-53082576-CCCGCCG-C is described in ClinVar as [Likely_benign]. Clinvar id is 810606.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-53082576-CCCGCCG-C is described in Lovd as [Likely_benign].

BS2

High Hemizygotes in GnomAd4 at 22 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TSPYL2	NM_022117.4 link	c.95_100delCGCCGC	p.Pro32_Pro33del	disruptive_inframe_deletion	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.95_100delCGCCGC	p.Pro32_Pro33del	disruptive_inframe_deletion	Exon 1 of 7	1	NM_022117.4	ENSP00000364591.4	Q9H2G4
TSPYL2	ENST00000579390.1 link	c.95_100delCGCCGC	p.Pro32_Pro33del	disruptive_inframe_deletion	Exon 1 of 3	5		ENSP00000462287.1	J3KS33
TSPYL2	ENST00000553557.5 link	n.227_232delCGCCGC		non_coding_transcript_exon_variant	Exon 1 of 4	2

Frequencies

GnomAD3 genomes

AF:

0.000740

AC:

AN:

110857

Hom.:

Cov.:

AF XY:

0.000660

AC XY:

AN XY:

33333

show subpopulations

Gnomad AFR

AF:

0.000557

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000378

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000574

Gnomad SAS

AF:

0.00147

Gnomad FIN

AF:

0.000171

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000988

Gnomad OTH

AF:

0.00134

GnomAD3 exomes

AF:

0.000872

AC:

AN:

66535

Hom.:

AF XY:

0.000505

AC XY:

AN XY:

21791

show subpopulations

Gnomad AFR exome

AF:

0.000376

Gnomad AMR exome

AF:

0.000634

Gnomad ASJ exome

AF:

0.000459

Gnomad EAS exome

AF:

0.00101

Gnomad SAS exome

AF:

0.000497

Gnomad FIN exome

AF:

0.00209

Gnomad NFE exome

AF:

0.00113

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000910

AC:

943

AN:

1036105

Hom.:

AF XY:

0.000778

AC XY:

262

AN XY:

336727

show subpopulations

Gnomad4 AFR exome

AF:

0.000288

Gnomad4 AMR exome

AF:

0.000405

Gnomad4 ASJ exome

AF:

0.000110

Gnomad4 EAS exome

AF:

0.000598

Gnomad4 SAS exome

AF:

0.000572

Gnomad4 FIN exome

AF:

0.00129

Gnomad4 NFE exome

AF:

0.000980

Gnomad4 OTH exome

AF:

0.000913

GnomAD4 genome

AF:

0.000740

AC:

AN:

110884

Hom.:

Cov.:

AF XY:

0.000659

AC XY:

AN XY:

33372

show subpopulations

Gnomad4 AFR

AF:

0.000556

Gnomad4 AMR

AF:

0.000377

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000577

Gnomad4 SAS

AF:

0.00148

Gnomad4 FIN

AF:

0.000171

Gnomad4 NFE

AF:

0.000988

Gnomad4 OTH

AF:

0.00132

Bravo

AF:

0.000631

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

May 01, 2018

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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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.

X-53082576-CCCGCCGCCGCCG-CCCGCCG

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