Variant chrX-49304864-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001098413.4(GAGE10):c.5G>A(p.Ser2Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000324 in 1,205,736 control chromosomes in the GnomAD database, including 1 homozygotes. There are 105 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00022 ( 0 hom., 4 hem., cov: 26)

Exomes 𝑓: 0.00033 ( 1 hom. 101 hem. )

Consequence

GAGE10
NM_001098413.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.695

Variant links:

Genes affected

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

GAGE10 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.11329302).

BS2

High Hemizygotes in GnomAd4 at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GAGE10	NM_001098413.4 linkuse as main transcript	c.5G>A	p.Ser2Asn	missense_variant	2/5	ENST00000407599.4	NP_001091883.3	A6NGK3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GAGE10	ENST00000407599.4 linkuse as main transcript	c.5G>A	p.Ser2Asn	missense_variant	2/5	5	NM_001098413.4	ENSP00000385415.3		A6NGK3

Frequencies

GnomAD3 genomes

AF:

0.000221

AC:

AN:

113028

Hom.:

Cov.:

AF XY:

0.000114

AC XY:

AN XY:

35154

show subpopulations

Gnomad AFR

AF:

0.0000964

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:

0.000393

Gnomad OTH

AF:

0.000657

GnomAD3 exomes

AF:

0.000148

AC:

AN:

182814

Hom.:

AF XY:

0.000193

AC XY:

AN XY:

67368

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000293

Gnomad OTH exome

AF:

0.000662

GnomAD4 exome

AF:

0.000335

AC:

366

AN:

1092708

Hom.:

Cov.:

AF XY:

0.000281

AC XY:

101

AN XY:

360004

show subpopulations

Gnomad4 AFR exome

AF:

0.0000380

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000421

Gnomad4 OTH exome

AF:

0.000262

GnomAD4 genome

AF:

0.000221

AC:

AN:

113028

Hom.:

Cov.:

AF XY:

0.000114

AC XY:

AN XY:

35154

show subpopulations

Gnomad4 AFR

AF:

0.0000964

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000393

Gnomad4 OTH

AF:

0.000657

Alfa

AF:

0.000564

Hom.:

Bravo

AF:

0.000193

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000149

AC:

ExAC

AF:

0.0000906

AC:

EpiCase

AF:

0.000218

EpiControl

AF:

0.000415

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 submitter

clinical testing

Ambry Genetics

Jun 11, 2021

The c.5G>A (p.S2N) alteration is located in exon 2 (coding exon 1) of the GAGE10 gene. This alteration results from a G to A substitution at nucleotide position 5, causing the serine (S) at amino acid position 2 to be replaced by an asparagine (N). 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

0.23

BayesDel_addAF

Benign

-0.78

BayesDel_noAF

Benign

-1.1

CADD

Benign

5.8

DANN

Benign

0.86

FATHMM_MKL

Benign

0.049

M_CAP

Benign

0.00099

MetaRNN

Benign

0.11

MetaSVM

Benign

-0.97

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-1.7

REVEL

Benign

0.025

Sift

Benign

0.36

Sift4G

Benign

0.39

Vest4

0.13

MVP

0.36

MPC

0.0086

ClinPred

0.052

GERP RS

0.29

gMVP

0.018

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over