Genetic Variant GAGE12J:p.Pro26Ser (chrX-49323269-C-T) – ACMG Classification: Benign (-8 pts)

Variant summary

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

The NM_001098406.4(GAGE12J):c.76C>T(p.Pro26Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000664 in 1,144,884 control chromosomes in the GnomAD database, including 1 homozygotes. There are 31 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P26L) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000074 ( 0 hom., 3 hem., cov: 20)

Exomes 𝑓: 0.000066 ( 1 hom. 28 hem. )

Consequence

GAGE12J
NM_001098406.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0650

Publications

1 publications found

Variant links:

Genes affected

GAGE12J (HGNC:17778): (G antigen 12J)

GAGE12J 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=0.01904431).

BS2

High Hemizygotes in GnomAd4 at 3 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001098406.4. 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
	GAGE12J	NM_001098406.4	MANE Select	c.76C>T	p.Pro26Ser	missense	Exon 2 of 5	NP_001091876.2	A6NER3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GAGE12J	ENST00000442437.3	TSL:1 MANE Select	c.76C>T	p.Pro26Ser	missense	Exon 2 of 5	ENSP00000409832.2	A6NER3

Frequencies

GnomAD3 genomes

AF:

0.0000739

AC:

AN:

108278

Hom.:

Cov.:

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:

0.00226

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000139

AC:

AN:

165997

AF XY:

0.000123

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00173

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000656

AC:

AN:

1036559

Hom.:

Cov.:

AF XY:

0.0000870

AC XY:

AN XY:

321857

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

25960

American (AMR)

AF:

0.0000289

AC:

AN:

34643

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18718

East Asian (EAS)

AF:

0.00212

AC:

AN:

29741

South Asian (SAS)

AF:

0.00

AC:

AN:

52761

European-Finnish (FIN)

AF:

0.00

AC:

AN:

34669

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3527

European-Non Finnish (NFE)

AF:

0.00000126

AC:

AN:

792583

Other (OTH)

AF:

0.0000682

AC:

AN:

43957

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.405

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome 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

GnomAD4 genome

AF:

0.0000739

AC:

AN:

108325

Hom.:

Cov.:

AF XY:

0.0000953

AC XY:

AN XY:

31493

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30188

American (AMR)

AF:

0.00

AC:

AN:

10293

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2594

East Asian (EAS)

AF:

0.00227

AC:

AN:

3531

South Asian (SAS)

AF:

0.00

AC:

AN:

2599

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5599

Middle Eastern (MID)

AF:

0.00

AC:

AN:

208

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

51225

Other (OTH)

AF:

0.00

AC:

AN:

1449

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

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:

0.00

Hom.:

Bravo

AF:

0.000113

ExAC

AF:

0.000127

AC:

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

0.18

BayesDel_addAF

Benign

-0.83

BayesDel_noAF

Benign

-0.97

CADD

Benign

3.6

(source)

DANN

Uncertain

0.99

FATHMM_MKL

Benign

0.0064

M_CAP

Benign

0.0019

MetaRNN

Benign

0.019

MetaSVM

Benign

-1.1

PhyloP100

0.065

PROVEAN

Pathogenic

-4.6

REVEL

Benign

0.016

Sift

Benign

0.25

Sift4G

Benign

0.12

Vest4

0.097

MutPred

0.49

Gain of phosphorylation at P26 (P = 0.0123)

MVP

0.12

MPC

0.43

ClinPred

0.27

GERP RS

-0.057

gMVP

0.022

Mutation Taster

=100/0

polymorphism

(source)

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

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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