X-152135271-G-T

Position:

chrX-152135271-G-T

Variant summary

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

The NM_021048.5(MAGEA10):c.350C>A(p.Pro117Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000389 in 1,208,994 control chromosomes in the GnomAD database, including 1 homozygotes. There are 12 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000063 ( 1 hom., 1 hem., cov: 22)

Exomes 𝑓: 0.000036 ( 0 hom. 11 hem. )

Consequence

MAGEA10
NM_021048.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.133

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=0.050027013).

BS2

High Hemizygotes in GnomAdExome4 at 11 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAGEA10	NM_021048.5 linkuse as main transcript	c.350C>A	p.Pro117Gln	missense_variant	4/4	ENST00000370323.9	NP_066386.3	P43363B2RAE8
MAGEA10	NM_001011543.3 linkuse as main transcript	c.350C>A	p.Pro117Gln	missense_variant	5/5		NP_001011543.3	P43363B2RAE8
MAGEA10	NM_001251828.2 linkuse as main transcript	c.350C>A	p.Pro117Gln	missense_variant	5/5		NP_001238757.2	P43363B2RAE8
LOC100533997	NM_001204811.3 linkuse as main transcript	c.-278+3204C>A		intron_variant			NP_001191740.1	P43359

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAGEA10	ENST00000370323.9 linkuse as main transcript	c.350C>A	p.Pro117Gln	missense_variant	4/4	1	NM_021048.5	ENSP00000359347.4		P43363

Frequencies

GnomAD3 genomes

AF:

0.0000629

AC:

AN:

111248

Hom.:

Cov.:

AF XY:

0.0000299

AC XY:

AN XY:

33438

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000952

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00142

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000665

GnomAD3 exomes

AF:

0.0000328

AC:

AN:

182766

Hom.:

AF XY:

0.0000298

AC XY:

AN XY:

67226

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000144

Gnomad SAS exome

AF:

0.0000529

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000665

GnomAD4 exome

AF:

0.0000364

AC:

AN:

1097746

Hom.:

Cov.:

AF XY:

0.0000303

AC XY:

AN XY:

363116

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000199

Gnomad4 SAS exome

AF:

0.0000185

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000119

Gnomad4 OTH exome

AF:

0.000695

GnomAD4 genome

AF:

0.0000629

AC:

AN:

111248

Hom.:

Cov.:

AF XY:

0.0000299

AC XY:

AN XY:

33438

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000952

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00142

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000665

Bravo

AF:

0.0000491

ExAC

AF:

0.0000330

AC:

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

May 25, 2022

The c.350C>A (p.P117Q) alteration is located in exon 5 (coding exon 1) of the MAGEA10 gene. This alteration results from a C to A substitution at nucleotide position 350, causing the proline (P) at amino acid position 117 to be replaced by a glutamine (Q). 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

0.11

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.80

CADD

Benign

DANN

Benign

0.75

DEOGEN2

Benign

0.020

T;T;T;T

FATHMM_MKL

Benign

0.043

LIST_S2

Benign

0.29

.;T;T;T

M_CAP

Benign

0.013

MetaRNN

Benign

0.050

T;T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Pathogenic

3.1

M;M;.;.

PrimateAI

Benign

0.24

PROVEAN

Pathogenic

-5.4

D;D;D;D

REVEL

Benign

0.022

Sift

Benign

0.045

D;D;D;D

Sift4G

Uncertain

0.0080

D;D;.;.

Polyphen

0.61

P;P;.;.

Vest4

0.053

MutPred

0.25

Loss of glycosylation at P117 (P = 0.018);Loss of glycosylation at P117 (P = 0.018);Loss of glycosylation at P117 (P = 0.018);Loss of glycosylation at P117 (P = 0.018);

MVP

0.22

MPC

0.25

ClinPred

0.25

GERP RS

-1.4

Varity_R

0.24

gMVP

0.14

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