chrX-53082879-C-G

Variant names:

• chrX-53082879-C-G
• rs782528598
• NM_022117.4:c.381C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_022117.4(TSPYL2):​c.381C>G​(p.Ser127Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 22)
  • Exomes 𝑓: 9.1e-7 (0 hom. 1 hem.)
  • Failed GnomAD Quality Control
• Consequence: TSPYL2 NM_022117.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0460
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20047778).

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.381C>G	p.Ser127Arg	missense	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.381C>G	p.Ser127Arg	missense	Exon 1 of 7	ENSP00000364591.4	Q9H2G4
	TSPYL2	ENST00000912653.1		c.381C>G	p.Ser127Arg	missense	Exon 1 of 7	ENSP00000582712.1
	TSPYL2	ENST00000887608.1		c.381C>G	p.Ser127Arg	missense	Exon 1 of 7	ENSP00000557667.1

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 9.11e-7 AC: 1 AN: 1097330 Hom.: 0 Cov.: 33 AF XY: 0.00000276 AC XY: 1 AN XY: 362830

African (AFR) AF: 0.00 AC: 0 AN: 26392

American (AMR) AF: 0.0000285 AC: 1 AN: 35136

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19362

East Asian (EAS) AF: 0.00 AC: 0 AN: 30188

South Asian (SAS) AF: 0.00 AC: 0 AN: 53994

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40285

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4132

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 841792

Other (OTH) AF: 0.00 AC: 0 AN: 46049

GnomAD4 genome Cov.: 22

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.45
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.30	T
FATHMM_MKL	Benign	0.24	N
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.028	D
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		0.046
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.042
Sift	Uncertain	0.015	D
Sift4G	Benign	0.065	T
Polyphen		0.98	D
Vest4		0.29
MutPred		0.25		Loss of glycosylation at S127 (P = 0.027)
MVP		0.082
MPC		0.85
ClinPred		0.56	D
GERP RS		2.6
PromoterAI		0.0057	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.19
gMVP		0.25
Mutation Taster		=98/2	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: rs782528598; hg19: chrX-53112061;