X-53082576-CCCGCCGCCGCCG-CCCGCCGCCGCCGCCGCCG

Variant names:

• chrX-53082576-C-CCCGCCG
• rs781884842
• NM_022117.4:c.95_100dupCGCCGC

Variant summary

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

The NM_022117.4(TSPYL2):​c.95_100dupCGCCGC​(p.Pro32_Pro33dup) variant causes a disruptive inframe insertion change. The variant allele was found at a frequency of 0.00129 in 1,146,877 control chromosomes in the GnomAD database, including 6 homozygotes. There are 304 hemizygotes in GnomAD. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0017 (1 hom., 48 hem., cov: 23)
  • Exomes 𝑓: 0.0012 (5 hom. 256 hem.)
• Consequence: TSPYL2 NM_022117.4 disruptive_inframe_insertion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.25

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]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BS2: High Hemizygotes in GnomAd4 at 48 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TSPYL2	NM_022117.4	c.95_100dupCGCCGC	p.Pro32_Pro33dup	disruptive_inframe_insertion	Exon 1 of 7	ENST00000375442.8	NP_071400.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TSPYL2	ENST00000375442.8	c.95_100dupCGCCGC	p.Pro32_Pro33dup	disruptive_inframe_insertion	Exon 1 of 7	1	NM_022117.4	ENSP00000364591.4
TSPYL2	ENST00000579390.1	c.95_100dupCGCCGC	p.Pro32_Pro33dup	disruptive_inframe_insertion	Exon 1 of 3	5		ENSP00000462287.1
TSPYL2	ENST00000553557.5	n.227_232dupCGCCGC		non_coding_transcript_exon_variant	Exon 1 of 4	2

Frequencies

GnomAD3 genomes AF: 0.00169 AC: 187 AN: 110856 Hom.: 1 Cov.: 23 AF XY: 0.00135 AC XY: 45 AN XY: 33330

Gnomad AFR AF: 0.00242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00179

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00368

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00158

Gnomad OTH AF: 0.000670

GnomAD3 exomes AF: 0.00150 AC: 100 AN: 66535 Hom.: 1 AF XY: 0.000551 AC XY: 12 AN XY: 21791

Gnomad AFR exome AF: 0.00225

Gnomad AMR exome AF: 0.00317

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000604

Gnomad SAS exome AF: 0.000398

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00163

Gnomad OTH exome AF: 0.00144

GnomAD4 exome AF: 0.00125 AC: 1290 AN: 1035994 Hom.: 5 Cov.: 32 AF XY: 0.000761 AC XY: 256 AN XY: 336598

Gnomad4 AFR exome AF: 0.00189

Gnomad4 AMR exome AF: 0.00332

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000336

Gnomad4 SAS exome AF: 0.000941

Gnomad4 FIN exome AF: 0.000174

Gnomad4 NFE exome AF: 0.00128

Gnomad4 OTH exome AF: 0.00112

GnomAD4 genome AF: 0.00171 AC: 190 AN: 110883 Hom.: 1 Cov.: 23 AF XY: 0.00144 AC XY: 48 AN XY: 33369

Gnomad4 AFR AF: 0.00252

Gnomad4 AMR AF: 0.00179

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00370

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00158

Gnomad4 OTH AF: 0.000661

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs781884842; hg19: chrX-53111758;