rs751679256

Variant names:

Variant summary

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

The NM_021048.5(MAGEA10):c.1042A>G(p.Thr348Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000191 in 1,204,623 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000090 ( 0 hom., 1 hem., cov: 21)

Exomes 𝑓: 0.000020 ( 0 hom. 3 hem. )

Consequence

MAGEA10
NM_021048.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.47

Variant links:

Genes affected

MAGEA10 (HGNC:6797): (MAGE family member A10) This gene is a member of the MAGEA gene family. The members of this family encode proteins with 50 to 80% sequence identity to each other. The promoters and first exons of the MAGEA genes show considerable variability, suggesting that the existence of this gene family enables the same function to be expressed under different transcriptional controls. The MAGEA genes are clustered at chromosomal location Xq28. They have been implicated in some hereditary disorders, such as dyskeratosis congenita. Alternative splicing results in multiple transcript variants. Read-through transcription also exists between this gene and the downstream melanoma antigen family A, 5 (MAGEA5) gene.[provided by RefSeq, Oct 2011]

MAGEA10 links:

LOC100533997 (HGNC:):

LOC100533997 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=0.04732099).

BS2

High Hemizygotes in GnomAdExome4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAGEA10	NM_021048.5 link	c.1042A>G	p.Thr348Ala	missense_variant	Exon 4 of 4	ENST00000370323.9	NP_066386.3	P43363B2RAE8
MAGEA10	NM_001011543.3 link	c.1042A>G	p.Thr348Ala	missense_variant	Exon 5 of 5		NP_001011543.3	P43363B2RAE8
MAGEA10	NM_001251828.2 link	c.1042A>G	p.Thr348Ala	missense_variant	Exon 5 of 5		NP_001238757.2	P43363B2RAE8
LOC100533997	NM_001204811.3 link	c.-278+3896A>G		intron_variant	Intron 1 of 3		NP_001191740.1	P43359

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAGEA10	ENST00000370323.9 link	c.1042A>G	p.Thr348Ala	missense_variant	Exon 4 of 4	1	NM_021048.5	ENSP00000359347.4		P43363

Frequencies

GnomAD3 genomes

AF:

0.00000901

AC:

AN:

111007

Hom.:

Cov.:

AF XY:

0.0000301

AC XY:

AN XY:

33203

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000189

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000201

AC:

AN:

1093616

Hom.:

Cov.:

AF XY:

0.00000836

AC XY:

AN XY:

359044

show subpopulations

Gnomad4 AFR exome

AF:

0.00

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:

0.0000263

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000901

AC:

AN:

111007

Hom.:

Cov.:

AF XY:

0.0000301

AC XY:

AN XY:

33203

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.0000189

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000416

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000346

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 20, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1042A>G (p.T348A) alteration is located in exon 5 (coding exon 1) of the MAGEA10 gene. This alteration results from a A to G substitution at nucleotide position 1042, causing the threonine (T) at amino acid position 348 to be replaced by an alanine (A). 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

0.070

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-1.1

CADD

Benign

0.16

DANN

Benign

0.81

DEOGEN2

Benign

0.010

T;T

FATHMM_MKL

Benign

0.0034

LIST_S2

Benign

0.096

.;T

M_CAP

Benign

0.0030

MetaRNN

Benign

0.047

T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

1.4

L;L

PrimateAI

Benign

0.25

PROVEAN

Benign

-0.97

N;N

REVEL

Benign

0.014

Sift

Benign

0.61

T;T

Sift4G

Benign

0.77

T;T

Polyphen

0.053

B;B

Vest4

0.042

MutPred

0.19

Gain of relative solvent accessibility (P = 0.0166);Gain of relative solvent accessibility (P = 0.0166);

MVP

0.34

MPC

0.097

ClinPred

0.022

GERP RS

-3.7

Varity_R

0.047

gMVP

0.11

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