X-52813173-C-T

Position:

• chrX-52813173-C-T

Variant summary

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

The NM_001386970.1(XAGE5):​c.106C>T​(p.Pro36Ser) 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. 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.

• Frequency: Genomes: not found (cov: 23)
• Consequence: XAGE5 NM_001386970.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0980

Genes affected

XAGE5 (HGNC:30930): (X antigen family member 5) This gene is a member of the XAGE subfamily, which belongs to the GAGE family. The GAGE genes are expressed in a variety of tumors and in some fetal and reproductive tissues. The protein encoded by this gene shares a sequence similarity with other GAGE/PAGE proteins. Because of the expression pattern and the sequence similarity, this protein also belongs to a family of CT (cancer-testis) antigens. [provided by RefSeq, Jul 2008]

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=0.10323024).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
XAGE5	NM_001386970.1	c.106C>T	p.Pro36Ser	missense_variant	4/6	ENST00000375501.2	NP_001373899.1
XAGE5	NM_130775.3	c.106C>T	p.Pro36Ser	missense_variant	3/5		NP_570131.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
XAGE5	ENST00000375501.2	c.106C>T	p.Pro36Ser	missense_variant	4/6	5	NM_001386970.1	ENSP00000364651.1
XAGE5	ENST00000375503.7	n.106C>T		non_coding_transcript_exon_variant	2/5	1		ENSP00000364653.3

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 23

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

Sep 09, 2024

The c.106C>T (p.P36S) alteration is located in exon 3 (coding exon 2) of the XAGE5 gene. This alteration results from a C to T substitution at nucleotide position 106, causing the proline (P) at amino acid position 36 to be replaced by a serine (S). 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	0.095
BayesDel_addAF	Benign	-0.45	T
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.4
DANN	Benign	0.34
DEOGEN2	Benign	0.036	T;T
FATHMM_MKL	Benign	0.0018	N
LIST_S2	Benign	0.62	T;.
M_CAP	Benign	0.00044	T
MetaRNN	Benign	0.10	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	2.0	M;M
PrimateAI	Benign	0.32	T
PROVEAN	Pathogenic	-5.8	D;D
REVEL	Benign	0.041
Sift	Benign	0.079	T;T
Sift4G	Uncertain	0.036	D;D
Polyphen		0.013	B;B
Vest4		0.21
MutPred		0.52		Loss of catalytic residue at P36 (P = 0.0019);Loss of catalytic residue at P36 (P = 0.0019);
MVP		0.030
MPC		0.0028
ClinPred		0.080	T
GERP RS		-2.2
Varity_R		0.099
gMVP		0.025

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-52842197;