X-52818208-C-G

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001386970.1(XAGE5):​c.322C>G​(p.Leu108Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000455 in 1,210,100 control chromosomes in the GnomAD database, including 2 homozygotes. There are 10 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00028 ( 2 hom., 4 hem., cov: 23)
Exomes 𝑓: 0.000022 ( 0 hom. 6 hem. )

Consequence

XAGE5
NM_001386970.1 missense

Scores

17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -2.34
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.004954785).
BS2
High Homozygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
XAGE5NM_001386970.1 linkc.322C>G p.Leu108Val missense_variant Exon 6 of 6 ENST00000375501.2 NP_001373899.1
XAGE5NM_130775.3 linkc.322C>G p.Leu108Val missense_variant Exon 5 of 5 NP_570131.1 Q8WWM1Q3SY49

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
XAGE5ENST00000375501.2 linkc.322C>G p.Leu108Val missense_variant Exon 6 of 6 5 NM_001386970.1 ENSP00000364651.1 Q8WWM1
XAGE5ENST00000375503.7 linkn.*250C>G non_coding_transcript_exon_variant Exon 5 of 5 1 ENSP00000364653.3 Q3SY49
XAGE5ENST00000375503.7 linkn.*250C>G 3_prime_UTR_variant Exon 5 of 5 1 ENSP00000364653.3 Q3SY49
XAGE5ENST00000445860.2 linkn.325C>G non_coding_transcript_exon_variant Exon 2 of 2 3

Frequencies

GnomAD3 genomes
AF:
0.000276
AC:
31
AN:
112516
Hom.:
2
Cov.:
23
AF XY:
0.000115
AC XY:
4
AN XY:
34664
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.0381
Gnomad AMR
AF:
0.00
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:
0.0000937
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000219
AC:
4
AN:
182662
Hom.:
0
AF XY:
0.0000446
AC XY:
3
AN XY:
67270
show subpopulations
Gnomad AFR exome
AF:
0.00
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:
0.0000491
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000219
AC:
24
AN:
1097584
Hom.:
0
Cov.:
29
AF XY:
0.0000165
AC XY:
6
AN XY:
363078
show subpopulations
Gnomad4 AFR exome
AF:
0.00
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:
0.0000261
Gnomad4 OTH exome
AF:
0.0000434
GnomAD4 genome
AF:
0.000276
AC:
31
AN:
112516
Hom.:
2
Cov.:
23
AF XY:
0.000115
AC XY:
4
AN XY:
34664
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000937
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.000385
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000149
AC:
1
ExAC
AF:
0.0000330
AC:
4

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Feb 19, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.322C>G (p.L108V) alteration is located in exon 5 (coding exon 4) of the XAGE5 gene. This alteration results from a C to G substitution at nucleotide position 322, causing the leucine (L) at amino acid position 108 to be replaced by a valine (V). 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
0.032
BayesDel_addAF
Benign
-0.68
T
BayesDel_noAF
Benign
-1.2
CADD
Benign
0.0070
DANN
Benign
0.094
DEOGEN2
Benign
0.012
T;T
FATHMM_MKL
Benign
0.00031
N
LIST_S2
Benign
0.34
T;.
M_CAP
Benign
0.00058
T
MetaRNN
Benign
0.0050
T;T
MetaSVM
Benign
-0.97
T
MutationAssessor
Benign
-1.7
N;N
PrimateAI
Benign
0.37
T
PROVEAN
Benign
0.60
N;N
REVEL
Benign
0.0050
Sift
Benign
1.0
T;T
Sift4G
Benign
1.0
T;T
Polyphen
0.0
B;B
Vest4
0.048
MVP
0.16
MPC
0.0028
ClinPred
0.021
T
GERP RS
-2.0
Varity_R
0.035
gMVP
0.0026

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs139024407; hg19: chrX-52847232; API