X-53082576-CCCGCCGCCGCCG-CCCGCCGCCG

Variant names:

• chrX-53082576-CCCG-C
• rs781884842
• NM_022117.4:c.98_100delCGC

Variant summary

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

The NM_022117.4(TSPYL2):​c.98_100delCGC​(p.Pro33del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.000475 in 1,100,532 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 6 hemizygotes in GnomAD. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000045 (0 hom., 1 hem., cov: 23)
  • Exomes 𝑓: 0.00052 (0 hom. 5 hem.)
• Consequence: TSPYL2 NM_022117.4 disruptive_inframe_deletion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.25
• Publications: 2 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 5 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.98_100delCGC	p.Pro33del	disruptive_inframe_deletion	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.98_100delCGC	p.Pro33del	disruptive_inframe_deletion	Exon 1 of 7	ENSP00000364591.4	Q9H2G4
	TSPYL2	ENST00000912653.1		c.98_100delCGC	p.Pro33del	disruptive_inframe_deletion	Exon 1 of 7	ENSP00000582712.1
	TSPYL2	ENST00000887608.1		c.98_100delCGC	p.Pro33del	disruptive_inframe_deletion	Exon 1 of 7	ENSP00000557667.1

Frequencies

GnomAD3 genomes AF: 0.0000451 AC: 5 AN: 110819 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000945

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000171

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000570

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00651 AC: 433 AN: 66535 AF XY: 0.000138

Gnomad AFR exome AF: 0.0222

Gnomad AMR exome AF: 0.00472

Gnomad ASJ exome AF: 0.00803

Gnomad EAS exome AF: 0.00805

Gnomad FIN exome AF: 0.00951

Gnomad NFE exome AF: 0.00615

Gnomad OTH exome AF: 0.00815

GnomAD4 exome AF: 0.000523 AC: 518 AN: 989691 Hom.: 0 AF XY: 0.0000158 AC XY: 5 AN XY: 315893

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00286 AC: 66 AN: 23067

American (AMR) AF: 0.00314 AC: 76 AN: 24202

Ashkenazi Jewish (ASJ) AF: 0.00183 AC: 31 AN: 16959

East Asian (EAS) AF: 0.00143 AC: 36 AN: 25126

South Asian (SAS) AF: 0.000529 AC: 23 AN: 43478

European-Finnish (FIN) AF: 0.00157 AC: 42 AN: 26788

Middle Eastern (MID) AF: 0.00138 AC: 4 AN: 2909

European-Non Finnish (NFE) AF: 0.000272 AC: 214 AN: 785643

Other (OTH) AF: 0.000626 AC: 26 AN: 41519

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0000451 AC: 5 AN: 110841 Hom.: 0 Cov.: 23 AF XY: 0.0000300 AC XY: 1 AN XY: 33351

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 30584

American (AMR) AF: 0.0000944 AC: 1 AN: 10598

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2637

East Asian (EAS) AF: 0.00 AC: 0 AN: 3469

South Asian (SAS) AF: 0.00 AC: 0 AN: 2703

European-Finnish (FIN) AF: 0.000171 AC: 1 AN: 5845

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 209

European-Non Finnish (NFE) AF: 0.0000570 AC: 3 AN: 52614

Other (OTH) AF: 0.00 AC: 0 AN: 1511

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.0658340), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.0184 Hom.: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		4.3
Mutation Taster		=91/9	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs781884842; hg19: chrX-53111758; COSMIC: COSV60238417; COSMIC: COSV60238417;