Variant X-49304939-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001098413.4(GAGE10):c.80T>G(p.Leu27Arg) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000283 in 1,199,468 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 10 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 0.000089 ( 0 hom., 3 hem., cov: 24)

Exomes 𝑓: 0.000022 ( 0 hom. 7 hem. )

Consequence

GAGE10
NM_001098413.4 missense, splice_region

Scores

Splicing: ADA: 0.00001390

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: -0.0580

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 Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.03757626).

BS2

High Hemizygotes in GnomAd4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GAGE10	NM_001098413.4 link	c.80T>G	p.Leu27Arg	missense_variant, splice_region_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 link	c.80T>G	p.Leu27Arg	missense_variant, splice_region_variant	2/5	5	NM_001098413.4	ENSP00000385415.3		A6NGK3

Frequencies

GnomAD3 genomes

AF:

0.0000887

AC:

AN:

112725

Hom.:

Cov.:

AF XY:

0.0000860

AC XY:

AN XY:

34881

show subpopulations

Gnomad AFR

AF:

0.000193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000554

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000375

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000117

AC:

AN:

179168

Hom.:

AF XY:

0.0000935

AC XY:

AN XY:

64146

show subpopulations

Gnomad AFR exome

AF:

0.0000768

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00102

Gnomad SAS exome

AF:

0.000169

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000372

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000221

AC:

AN:

1086743

Hom.:

Cov.:

AF XY:

0.0000197

AC XY:

AN XY:

354629

show subpopulations

Gnomad4 AFR exome

AF:

0.0000383

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000265

Gnomad4 SAS exome

AF:

0.0000565

Gnomad4 FIN exome

AF:

0.0000247

Gnomad4 NFE exome

AF:

0.0000132

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000887

AC:

AN:

112725

Hom.:

Cov.:

AF XY:

0.0000860

AC XY:

AN XY:

34881

show subpopulations

Gnomad4 AFR

AF:

0.000193

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000554

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000375

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000434

Hom.:

Bravo

AF:

0.0000604

ExAC

AF:

0.000107

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 29, 2023

The c.80T>G (p.L27R) alteration is located in exon 2 (coding exon 1) of the GAGE10 gene. This alteration results from a T to G substitution at nucleotide position 80, causing the leucine (L) at amino acid position 27 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.057

BayesDel_addAF

Benign

-0.82

BayesDel_noAF

Benign

-1.0

CADD

Benign

7.5

DANN

Benign

0.41

FATHMM_MKL

Benign

0.0052

M_CAP

Benign

0.0016

MetaRNN

Benign

0.038

MetaSVM

Benign

-0.92

PrimateAI

Benign

0.37

PROVEAN

Uncertain

-3.9

REVEL

Benign

0.043

Sift

Benign

0.31

Sift4G

Benign

0.47

Vest4

0.12

MVP

0.088

MPC

0.0074

ClinPred

0.0080

GERP RS

-1.6

gMVP

0.019

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000014

dbscSNV1_RF

Benign

0.0020

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