Variant X-49305491-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001098413.4(GAGE10):c.169G>A(p.Glu57Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000673 in 1,188,638 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000045 ( 0 hom., 1 hem., cov: 29)

Exomes 𝑓: 0.0000028 ( 0 hom. 1 hem. )

Consequence

GAGE10
NM_001098413.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.847

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 -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.07753223).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GAGE10	NM_001098413.4 linkuse as main transcript	c.169G>A	p.Glu57Lys	missense_variant	3/5	ENST00000407599.4	NP_001091883.3	A6NGK3
GAGE10	XM_024452325.1 linkuse as main transcript	c.127G>A	p.Glu43Lys	missense_variant	1/3		XP_024308093.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GAGE10	ENST00000407599.4 linkuse as main transcript	c.169G>A	p.Glu57Lys	missense_variant	3/5	5	NM_001098413.4	ENSP00000385415.3		A6NGK3

Frequencies

GnomAD3 genomes

AF:

0.0000453

AC:

AN:

110438

Hom.:

Cov.:

AF XY:

0.0000305

AC XY:

AN XY:

32830

show subpopulations

Gnomad AFR

AF:

0.0000343

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000285

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:

0.000669

GnomAD4 exome

AF:

0.00000278

AC:

AN:

1078200

Hom.:

Cov.:

AF XY:

0.00000283

AC XY:

AN XY:

353900

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000890

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000453

AC:

AN:

110438

Hom.:

Cov.:

AF XY:

0.0000305

AC XY:

AN XY:

32830

show subpopulations

Gnomad4 AFR

AF:

0.0000343

Gnomad4 AMR

AF:

0.000285

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000669

Alfa

AF:

0.0000843

Hom.:

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

Nov 21, 2023

The c.169G>A (p.E57K) alteration is located in exon 3 (coding exon 2) of the GAGE10 gene. This alteration results from a G to A substitution at nucleotide position 169, causing the glutamic acid (E) at amino acid position 57 to be replaced by a lysine (K). 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

0.096

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.55

DANN

Benign

0.45

FATHMM_MKL

Benign

0.0046

M_CAP

Benign

0.0015

MetaRNN

Benign

0.078

MetaSVM

Benign

-1.0

PrimateAI

Benign

0.40

PROVEAN

Benign

-2.3

REVEL

Benign

0.010

Sift

Benign

0.28

Sift4G

Benign

0.23

Vest4

0.064

MutPred

0.36

Gain of ubiquitination at E57 (P = 9e-04);

MVP

0.21

MPC

0.0083

ClinPred

0.052

GERP RS

-0.71

gMVP

0.038

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