Genetic Variant GAGE10:p.Pro99Arg (chrX-49317256-C-G) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001098413.4(GAGE10):c.296C>G(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. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0011 ( 0 hom., 29 hem., cov: 22)

Exomes 𝑓: 0.0017 ( 4 hom. 548 hem. )

Consequence

GAGE10
NM_001098413.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.84

Publications

0 publications found

Variant links:

Genes affected

GAGE10 (HGNC:30968): (G antigen 10)

GAGE10 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.012978703).

BS2

High Hemizygotes in GnomAd4 at 29 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001098413.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GAGE10	NM_001098413.4	MANE Select	c.296C>G	p.Pro99Arg	missense	Exon 4 of 5	NP_001091883.3	A6NGK3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GAGE10	ENST00000407599.4	TSL:5 MANE Select	c.296C>G	p.Pro99Arg	missense	Exon 4 of 5	ENSP00000385415.3	A6NGK3

Frequencies

GnomAD3 genomes

AF:

0.00105

AC:

117

AN:

111324

Hom.:

Cov.:

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

GnomAD2 exomes

AF:

0.000960

AC:

176

AN:

183420

AF XY:

0.000987

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 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.:

Cov.:

AF XY:

0.00152

AC XY:

548

AN XY:

360412

show subpopulations

African (AFR)

AF:

0.000228

AC:

AN:

26313

American (AMR)

AF:

0.000370

AC:

AN:

35091

Ashkenazi Jewish (ASJ)

AF:

0.0000519

AC:

AN:

19265

East Asian (EAS)

AF:

0.00

AC:

AN:

30050

South Asian (SAS)

AF:

0.00

AC:

AN:

54098

European-Finnish (FIN)

AF:

0.00105

AC:

AN:

39921

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4116

European-Non Finnish (NFE)

AF:

0.00205

AC:

1718

AN:

839659

Other (OTH)

AF:

0.00133

AC:

AN:

45841

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.417

Heterozygous variant carriers

157

236

314

393

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

132

198

264

330

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00105

AC:

117

AN:

111375

Hom.:

Cov.:

AF XY:

0.000863

AC XY:

AN XY:

33585

show subpopulations

African (AFR)

AF:

0.000522

AC:

AN:

30635

American (AMR)

AF:

0.0000955

AC:

AN:

10475

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2645

East Asian (EAS)

AF:

0.00

AC:

AN:

3573

South Asian (SAS)

AF:

0.00

AC:

AN:

2610

European-Finnish (FIN)

AF:

0.000505

AC:

AN:

5940

Middle Eastern (MID)

AF:

0.00

AC:

AN:

218

European-Non Finnish (NFE)

AF:

0.00183

AC:

AN:

53066

Other (OTH)

AF:

0.00

AC:

AN:

1528

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.516

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000910

Hom.:

Bravo

AF:

0.000918

TwinsUK

AF:

0.00162

AC:

ALSPAC

AF:

0.00312

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000743

AC:

ExAC

AF:

0.00114

AC:

139

EpiCase

AF:

0.00136

EpiControl

AF:

0.00160

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.74

BayesDel_noAF

Benign

-0.85

CADD

Benign

7.0

(source)

DANN

Uncertain

0.99

FATHMM_MKL

Benign

0.0063

M_CAP

Benign

0.0019

MetaRNN

Benign

0.013

MetaSVM

Benign

-1.1

PhyloP100

-1.8

PrimateAI

Benign

0.26

PROVEAN

Pathogenic

-7.4

REVEL

Benign

0.039

Sift

Benign

0.049

Sift4G

Uncertain

0.0020

Vest4

0.25

MVP

0.048

MPC

0.044

ClinPred

0.10

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over