Genetic Variant GAGE12J:p.Arg28Trp (chrX-49323275-C-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001098406.4(GAGE12J):c.82C>T(p.Arg28Trp) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000787 in 1,144,268 control chromosomes in the GnomAD database, including 1 homozygotes. There are 4 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000092 ( 0 hom., 1 hem., cov: 20)

Exomes 𝑓: 0.0000077 ( 1 hom. 3 hem. )

Consequence

GAGE12J
NM_001098406.4 missense, splice_region

Scores

Splicing: ADA: 0.002013

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

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: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.115507245).

BS2

High Hemizygotes in GnomAdExome4 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.82C>T	p.Arg28Trp	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>T	p.Arg28Trp	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

GnomAD2 exomes

AF:

0.00000604

AC:

AN:

165639

AF XY:

0.00

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000133

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000772

AC:

AN:

1036085

Hom.:

Cov.:

AF XY:

0.00000934

AC XY:

AN XY:

321323

show subpopulations

African (AFR)

AF:

0.00

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:

0.0000190

AC:

AN:

52712

European-Finnish (FIN)

AF:

0.00

AC:

AN:

34355

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3533

European-Non Finnish (NFE)

AF:

0.00000757

AC:

AN:

792564

Other (OTH)

AF:

0.0000228

AC:

AN:

43928

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.442

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:

0.00000924

AC:

AN:

108183

Hom.:

Cov.:

AF XY:

0.0000319

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

Age Distribution

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:

0.00000756

ExAC

AF:

0.00000849

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

0.14

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.91

CADD

Benign

(source)

DANN

Uncertain

0.99

FATHMM_MKL

Benign

0.0015

M_CAP

Benign

0.0016

MetaRNN

Benign

0.12

MetaSVM

Benign

-1.0

PhyloP100

-1.6

PROVEAN

Benign

-0.40

REVEL

Benign

0.084

Sift

Benign

0.053

Sift4G

Uncertain

0.044

Vest4

0.19

MutPred

0.30

Gain of glycosylation at S33 (P = 0.1139)

MVP

0.092

MPC

0.28

ClinPred

0.35

GERP RS

-1.9

gMVP

0.021

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0020

dbscSNV1_RF

Benign

0.082

SpliceAI score (max)

0.020

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