X-53082563-A-G

Variant names:

• chrX-53082563-A-G
• rs1556807148
• NM_022117.4:c.65A>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_022117.4(TSPYL2):​c.65A>G​(p.Gln22Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000902 in 110,816 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: 𝑓 0.0000090 (0 hom., 0 hem., cov: 23)
• Consequence: TSPYL2 NM_022117.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.328

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.107480556).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TSPYL2	NM_022117.4	c.65A>G	p.Gln22Arg	missense_variant	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.65A>G	p.Gln22Arg	missense_variant	Exon 1 of 7	1	NM_022117.4	ENSP00000364591.4
TSPYL2	ENST00000579390.1	c.65A>G	p.Gln22Arg	missense_variant	Exon 1 of 3	5		ENSP00000462287.1
TSPYL2	ENST00000553557.5	n.197A>G		non_coding_transcript_exon_variant	Exon 1 of 4	2

Frequencies

GnomAD3 genomes AF: 0.00000902 AC: 1 AN: 110816 Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0 AN XY: 33330

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000941

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 32

GnomAD4 genome AF: 0.00000902 AC: 1 AN: 110816 Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0 AN XY: 33330

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.0000941

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jul 09, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.65A>G (p.Q22R) alteration is located in exon 1 (coding exon 1) of the TSPYL2 gene. This alteration results from a A to G substitution at nucleotide position 65, causing the glutamine (Q) at amino acid position 22 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.45	T
BayesDel_noAF	Benign	-0.88
CADD	Benign	6.7
DANN	Benign	0.96
DEOGEN2	Benign	0.25	T;T
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.38	T;T
M_CAP	Benign	0.069	D
MetaRNN	Benign	0.11	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N;.
PrimateAI	Pathogenic	0.84	D
PROVEAN	Benign	-0.70	N;.
REVEL	Benign	0.050
Sift	Uncertain	0.0010	D;.
Sift4G	Benign	0.43	T;T
Polyphen		0.0010	B;.
Vest4		0.084
MutPred		0.17		Gain of glycosylation at P21 (P = 0.0542);Gain of glycosylation at P21 (P = 0.0542);
MVP		0.093
MPC		0.28
ClinPred		0.10	T
GERP RS		1.0
Varity_R		0.17
gMVP		0.16

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

Publications

LitVar

Other links and lift over

dbSNP: rs1556807148; hg19: chrX-53111745;