X-53082778-T-G

Variant names:

• chrX-53082778-T-G
• rs782596856
• NM_022117.4:c.280T>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_022117.4(TSPYL2):​c.280T>G​(p.Cys94Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000924 in 1,082,360 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. C94F) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 22)
  • Exomes 𝑓: 9.2e-7 (0 hom. 0 hem.)
• Consequence: TSPYL2 NM_022117.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.479

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.022072226).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TSPYL2	NM_022117.4	c.280T>G	p.Cys94Gly	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.280T>G	p.Cys94Gly	missense_variant	Exon 1 of 7	1	NM_022117.4	ENSP00000364591.4
TSPYL2	ENST00000579390.1	c.168+112T>G		intron_variant	Intron 1 of 2	5		ENSP00000462287.1
TSPYL2	ENST00000553557.5	n.412T>G		non_coding_transcript_exon_variant	Exon 1 of 4	2
TSPYL2	ENST00000578306.5	n.-216T>G		upstream_gene_variant		5		ENSP00000462635.1

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD3 exomes AF: 0.00000678 AC: 1 AN: 147534 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 43360

Gnomad AFR exome AF: 0.0000999

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 9.24e-7 AC: 1 AN: 1082360 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 352772

Gnomad4 AFR exome AF: 0.0000388

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 22

ExAC AF: 0.00000830 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.047
BayesDel_addAF	Benign	-0.64	T
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.16
DANN	Benign	0.63
DEOGEN2	Benign	0.17	T
FATHMM_MKL	Benign	0.0039	N
LIST_S2	Benign	0.53	T
M_CAP	Benign	0.0059	T
MetaRNN	Benign	0.022	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-0.86	N
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	1.4	N
REVEL	Benign	0.019
Sift	Benign	1.0	T
Sift4G	Benign	0.56	T
Polyphen		0.0	B
Vest4		0.14
MutPred		0.32		Gain of disorder (P = 0.0263);
MVP		0.043
MPC		0.32
ClinPred		0.020	T
GERP RS		-0.74
Varity_R		0.058
gMVP		0.083

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: rs782596856; hg19: chrX-53111960;