X-53083063-C-G

Variant names:

• chrX-53083063-C-G
• NM_022117.4:c.565C>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.565C>G​(p.Arg189Gly) 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 21)
• Consequence: TSPYL2 NM_022117.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -3.60
• 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=0.13746926).

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.565C>G	p.Arg189Gly	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.565C>G	p.Arg189Gly	missense	Exon 1 of 7	ENSP00000364591.4	Q9H2G4
	TSPYL2	ENST00000578306.5	TSL:5	n.70C>G		non_coding_transcript_exon	Exon 1 of 6	ENSP00000462635.1	J3KST2
	TSPYL2	ENST00000912653.1		c.565C>G	p.Arg189Gly	missense	Exon 1 of 7	ENSP00000582712.1

Frequencies

GnomAD3 genomes Cov.: 21

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 21

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	Benign	0.34
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.098
DANN	Benign	0.77
DEOGEN2	Benign	0.40	T
FATHMM_MKL	Benign	0.045	N
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.81	L
PhyloP100		-3.6
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-0.31	N
REVEL	Benign	0.083
Sift	Benign	0.031	D
Sift4G	Benign	0.11	T
Polyphen		0.96	P
Vest4		0.24
MutPred		0.24		Loss of stability (P = 0.0459)
MVP		0.068
MPC		0.62
ClinPred		0.31	T
GERP RS		-8.1
Varity_R		0.066
gMVP		0.60
Mutation Taster		=100/0	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

hg19: chrX-53112245;