dbSNP rs781989610: GAGE12J:p.Arg28Gly (chrX-49323275-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001098406.4(GAGE12J):c.82C>G(p.Arg28Gly) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000175 in 1,144,269 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R28W) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000092 ( 0 hom., 0 hem., cov: 20)

Exomes 𝑓: 9.7e-7 ( 0 hom. 0 hem. )

Consequence

GAGE12J
NM_001098406.4 missense, splice_region

Scores

Splicing: ADA: 0.0003710

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.55

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: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.078223884).

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.82C>G	p.Arg28Gly	missense splice_region	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.82C>G	p.Arg28Gly	missense splice_region	Exon 2 of 5	ENSP00000409832.2	A6NER3

Frequencies

GnomAD3 genomes

AF:

0.00000924

AC:

AN:

108183

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000332

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

9.65e-7

AC:

AN:

1036086

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

321324

show subpopulations

African (AFR)

AF:

0.0000385

AC:

AN:

25952

American (AMR)

AF:

0.00

AC:

AN:

34608

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18707

East Asian (EAS)

AF:

0.00

AC:

AN:

29726

South Asian (SAS)

AF:

0.00

AC:

AN:

52712

European-Finnish (FIN)

AF:

0.00

AC:

AN:

34356

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3533

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

792564

Other (OTH)

AF:

0.00

AC:

AN:

43928

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00000924

AC:

AN:

108183

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

31357

show subpopulations

African (AFR)

AF:

0.0000332

AC:

AN:

30142

American (AMR)

AF:

0.00

AC:

AN:

10257

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2595

East Asian (EAS)

AF:

0.00

AC:

AN:

3536

South Asian (SAS)

AF:

0.00

AC:

AN:

2598

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5593

Middle Eastern (MID)

AF:

0.00

AC:

AN:

229

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

51158

Other (OTH)

AF:

0.00

AC:

AN:

1432

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.625

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000189

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.92

CADD

Benign

4.7

(source)

DANN

Benign

0.82

FATHMM_MKL

Benign

0.00016

M_CAP

Benign

0.0012

MetaRNN

Benign

0.078

MetaSVM

Benign

-1.0

PhyloP100

-1.6

PROVEAN

Benign

-0.80

REVEL

Benign

0.035

Sift

Benign

0.16

Sift4G

Benign

0.17

Vest4

0.086

MutPred

0.26

Gain of sheet (P = 0.0266)

MVP

0.067

MPC

0.19

ClinPred

0.15

GERP RS

-1.9

gMVP

0.019

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00037

dbscSNV1_RF

Benign

0.12

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over