Variant X-49305467-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001098413.4(GAGE10):c.145C>T(p.Arg49Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000181 in 110,200 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. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000018 ( 0 hom., 0 hem., cov: 29)

Exomes 𝑓: 0.000020 ( 0 hom. 2 hem. )

Failed GnomAD Quality Control

Consequence

GAGE10
NM_001098413.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.497

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 -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.060540706).

BP6

Variant X-49305467-C-T is Benign according to our data. Variant chrX-49305467-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3280454.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GAGE10	NM_001098413.4 linkuse as main transcript	c.145C>T	p.Arg49Cys	missense_variant	3/5	ENST00000407599.4	NP_001091883.3	A6NGK3
GAGE10	XM_024452325.1 linkuse as main transcript	c.103C>T	p.Arg35Cys	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.145C>T	p.Arg49Cys	missense_variant	3/5	5	NM_001098413.4	ENSP00000385415.3		A6NGK3

Frequencies

GnomAD3 genomes

AF:

0.0000181

AC:

AN:

110200

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

32612

show subpopulations

Gnomad AFR

AF:

0.0000686

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

GnomAD3 exomes

AF:

0.0000206

AC:

AN:

97056

Hom.:

AF XY:

0.0000425

AC XY:

AN XY:

23506

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000222

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000195

AC:

AN:

1074559

Hom.:

Cov.:

AF XY:

0.00000570

AC XY:

AN XY:

351125

show subpopulations

Gnomad4 AFR exome

AF:

0.0000394

Gnomad4 AMR exome

AF:

0.0000592

Gnomad4 ASJ exome

AF:

0.000105

Gnomad4 EAS exome

AF:

0.000100

Gnomad4 SAS exome

AF:

0.0000188

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000108

Gnomad4 OTH exome

AF:

0.0000660

GnomAD4 genome

AF:

0.0000181

AC:

AN:

110200

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

32612

show subpopulations

Gnomad4 AFR

AF:

0.0000686

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:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 04, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.94

CADD

Benign

6.9

DANN

Benign

0.84

FATHMM_MKL

Benign

0.0011

M_CAP

Benign

0.0055

MetaRNN

Benign

0.061

MetaSVM

Benign

-0.99

PrimateAI

Benign

0.38

PROVEAN

Benign

-0.58

REVEL

Benign

0.012

Sift

Benign

0.060

Sift4G

Uncertain

0.043

Vest4

0.066

MutPred

0.26

Loss of solvent accessibility (P = 0.0703);

MVP

0.088

MPC

0.0074

ClinPred

0.035

GERP RS

-2.4

gMVP

0.014

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