X-53084808-G-T

Position:

• chrX-53084808-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The ENST00000375442.8(TSPYL2):​c.939G>T​(p.Gln313His) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 22)
• Consequence: TSPYL2 ENST00000375442.8 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.32

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]

TSPYL2 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3806833).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TSPYL2	NM_022117.4	c.939G>T	p.Gln313His	missense_variant	3/7	ENST00000375442.8	NP_071400.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TSPYL2	ENST00000375442.8	c.939G>T	p.Gln313His	missense_variant	3/7	1	NM_022117.4	ENSP00000364591.4
TSPYL2	ENST00000578306.5	n.*88G>T		non_coding_transcript_exon_variant	3/6	5		ENSP00000462635.1
TSPYL2	ENST00000578306.5	n.*88G>T		3_prime_UTR_variant	3/6	5		ENSP00000462635.1

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 22

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 16, 2022

The c.939G>T (p.Q313H) alteration is located in exon 3 (coding exon 3) of the TSPYL2 gene. This alteration results from a G to T substitution at nucleotide position 939, causing the glutamine (Q) at amino acid position 313 to be replaced by a histidine (H). 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	Uncertain	0.54
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Uncertain	24
DANN	Benign	0.95
DEOGEN2	Benign	0.17	T
FATHMM_MKL	Benign	0.61	D
LIST_S2	Benign	0.12	T
M_CAP	Benign	0.0097	T
MetaRNN	Benign	0.38	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.3	L
MutationTaster	Benign	0.95	N
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.18
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.054	T
Polyphen		1.0	D
Vest4		0.35
MutPred		0.60		Loss of stability (P = 0.1642);
MVP		0.068
MPC		0.87
ClinPred		0.63	D
GERP RS		2.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.25
gMVP		0.66

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-53113990;