X-53083056-C-CAGG

Variant names:

• chrX-53083056-C-CAGG
• rs1602102251
• NM_022117.4:c.562_564dupAGG

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_022117.4(TSPYL2):​c.562_564dupAGG​(p.Arg189dup) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000825 in 1,090,954 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 hemizygotes in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 22)
  • Exomes 𝑓: 0.0000082 (0 hom. 3 hem.)
• Consequence: TSPYL2 NM_022117.4 conservative_inframe_insertion
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.105
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BS2: High Hemizygotes in GnomAdExome4 at 3 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.562_564dupAGG	p.Arg189dup	conservative_inframe_insertion	Exon 1 of 7	NP_071400.1	Q9H2G4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSPYL2	ENST00000375442.8	TSL:1 MANE Select	c.562_564dupAGG	p.Arg189dup	conservative_inframe_insertion	Exon 1 of 7	ENSP00000364591.4	Q9H2G4
	TSPYL2	ENST00000578306.5	TSL:5	n.67_69dupAGG		non_coding_transcript_exon	Exon 1 of 6	ENSP00000462635.1	J3KST2
	TSPYL2	ENST00000912653.1		c.562_564dupAGG	p.Arg189dup	conservative_inframe_insertion	Exon 1 of 7	ENSP00000582712.1

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome AF: 0.00000825 AC: 9 AN: 1090954 Hom.: 0 Cov.: 31 AF XY: 0.00000840 AC XY: 3 AN XY: 357142

African (AFR) AF: 0.00 AC: 0 AN: 26264

American (AMR) AF: 0.00 AC: 0 AN: 34476

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19307

East Asian (EAS) AF: 0.0000333 AC: 1 AN: 30020

South Asian (SAS) AF: 0.00 AC: 0 AN: 53414

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39846

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4117

European-Non Finnish (NFE) AF: 0.00000478 AC: 4 AN: 837655

Other (OTH) AF: 0.0000872 AC: 4 AN: 45855

GnomAD4 genome Cov.: 22

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.10

Splicing

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

Other links and lift over

dbSNP: rs1602102251; hg19: chrX-53112238;