X-49317256-C-G

Variant summary

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

The NM_001098413.4(GAGE10):ā€‹c.296C>Gā€‹(p.Pro99Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00162 in 1,205,729 control chromosomes in the GnomAD database, including 4 homozygotes. There are 577 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 11/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.0011 ( 0 hom., 29 hem., cov: 22)
Exomes š‘“: 0.0017 ( 4 hom. 548 hem. )

Consequence

GAGE10
NM_001098413.4 missense

Scores

1
2
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.84
Variant links:
Genes affected
GAGE10 (HGNC:30968): (G antigen 10)

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=0.012978703).
BS2
High Hemizygotes in GnomAd4 at 29 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
GAGE10NM_001098413.4 linkuse as main transcriptc.296C>G p.Pro99Arg missense_variant 4/5 ENST00000407599.4 NP_001091883.3 A6NGK3
GAGE10XM_024452325.1 linkuse as main transcriptc.254C>G p.Pro85Arg missense_variant 2/3 XP_024308093.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
GAGE10ENST00000407599.4 linkuse as main transcriptc.296C>G p.Pro99Arg missense_variant 4/55 NM_001098413.4 ENSP00000385415.3 A6NGK3

Frequencies

GnomAD3 genomes
AF:
0.00105
AC:
117
AN:
111324
Hom.:
0
Cov.:
22
AF XY:
0.000865
AC XY:
29
AN XY:
33524
show subpopulations
Gnomad AFR
AF:
0.000523
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000956
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.000505
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00183
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000960
AC:
176
AN:
183420
Hom.:
0
AF XY:
0.000987
AC XY:
67
AN XY:
67882
show subpopulations
Gnomad AFR exome
AF:
0.000228
Gnomad AMR exome
AF:
0.000255
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.000750
Gnomad NFE exome
AF:
0.00183
Gnomad OTH exome
AF:
0.000883
GnomAD4 exome
AF:
0.00168
AC:
1841
AN:
1094354
Hom.:
4
Cov.:
30
AF XY:
0.00152
AC XY:
548
AN XY:
360412
show subpopulations
Gnomad4 AFR exome
AF:
0.000228
Gnomad4 AMR exome
AF:
0.000370
Gnomad4 ASJ exome
AF:
0.0000519
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00105
Gnomad4 NFE exome
AF:
0.00205
Gnomad4 OTH exome
AF:
0.00133
GnomAD4 genome
AF:
0.00105
AC:
117
AN:
111375
Hom.:
0
Cov.:
22
AF XY:
0.000863
AC XY:
29
AN XY:
33585
show subpopulations
Gnomad4 AFR
AF:
0.000522
Gnomad4 AMR
AF:
0.0000955
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.000505
Gnomad4 NFE
AF:
0.00183
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000910
Hom.:
7
Bravo
AF:
0.000918
TwinsUK
AF:
0.00162
AC:
6
ALSPAC
AF:
0.00312
AC:
9
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000743
AC:
5
ExAC
AF:
0.00114
AC:
139
EpiCase
AF:
0.00136
EpiControl
AF:
0.00160

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 submitterclinical testingAmbry GeneticsJun 17, 2024The c.296C>G (p.P99R) alteration is located in exon 4 (coding exon 3) of the GAGE10 gene. This alteration results from a C to G substitution at nucleotide position 296, causing the proline (P) at amino acid position 99 to be replaced by an arginine (R). 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
0.11
BayesDel_addAF
Benign
-0.74
T
BayesDel_noAF
Benign
-0.85
CADD
Benign
7.0
DANN
Uncertain
0.99
FATHMM_MKL
Benign
0.0063
N
M_CAP
Benign
0.0019
T
MetaRNN
Benign
0.013
T
MetaSVM
Benign
-1.1
T
PrimateAI
Benign
0.26
T
PROVEAN
Pathogenic
-7.4
D
REVEL
Benign
0.039
Sift
Benign
0.049
D
Sift4G
Uncertain
0.0020
D
Vest4
0.25
MVP
0.048
MPC
0.044
ClinPred
0.10
T
GERP RS
0.65
gMVP
0.011

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

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

Other links and lift over

dbSNP: rs139959382; hg19: chrX-49173735; API