Variant chrX-52813144-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001386970.1(XAGE5):c.77C>A(p.Pro26His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000877 in 1,208,218 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 42 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000054 ( 0 hom., 3 hem., cov: 23)

Exomes 𝑓: 0.000091 ( 0 hom. 39 hem. )

Consequence

XAGE5
NM_001386970.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0830

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]

XAGE5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.18460643).

BS2

High Hemizygotes in GnomAd4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
XAGE5	NM_001386970.1 linkuse as main transcript	c.77C>A	p.Pro26His	missense_variant	4/6	ENST00000375501.2	NP_001373899.1
XAGE5	NM_130775.3 linkuse as main transcript	c.77C>A	p.Pro26His	missense_variant	3/5		NP_570131.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
XAGE5	ENST00000375501.2 linkuse as main transcript	c.77C>A	p.Pro26His	missense_variant	4/6	5	NM_001386970.1	ENSP00000364651	P1
XAGE5	ENST00000375503.7 linkuse as main transcript	c.77C>A	p.Pro26His	missense_variant, NMD_transcript_variant	2/5	1		ENSP00000364653

Frequencies

GnomAD3 genomes

AF:

0.0000541

AC:

AN:

110949

Hom.:

Cov.:

AF XY:

0.0000904

AC XY:

AN XY:

33191

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

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:

0.000113

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000712

AC:

AN:

182531

Hom.:

AF XY:

0.0000893

AC XY:

AN XY:

67157

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:

0.000160

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000911

AC:

100

AN:

1097269

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

362749

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:

0.0000924

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000963

Gnomad4 OTH exome

AF:

0.000195

GnomAD4 genome

AF:

0.0000541

AC:

AN:

110949

Hom.:

Cov.:

AF XY:

0.0000904

AC XY:

AN XY:

33191

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:

0.000113

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000142

Hom.:

Bravo

AF:

0.0000604

ExAC

AF:

0.0000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 26, 2022

The c.77C>A (p.P26H) alteration is located in exon 3 (coding exon 2) of the XAGE5 gene. This alteration results from a C to A substitution at nucleotide position 77, causing the proline (P) at amino acid position 26 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

Benign

0.16

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.79

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.066

T;T

FATHMM_MKL

Benign

0.0061

LIST_S2

Benign

0.57

T;.

M_CAP

Benign

0.00063

MetaRNN

Benign

0.18

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

N;N

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.38

PROVEAN

Pathogenic

-6.3

D;D

REVEL

Benign

0.037

Sift

Uncertain

0.0090

D;D

Sift4G

Uncertain

0.0040

D;D

Polyphen

1.0

D;D

Vest4

0.27

MutPred

0.48

Loss of helix (P = 0.0237);Loss of helix (P = 0.0237);

MVP

0.055

MPC

0.0089

ClinPred

0.36

GERP RS

-0.023

Varity_R

0.34

gMVP

0.018

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over