Variant X-152134932-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_021048.5(MAGEA10):c.689T>C(p.Ile230Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00001 in 1,097,591 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 hemizygotes in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 22)

Exomes 𝑓: 0.000010 ( 0 hom. 3 hem. )

Consequence

MAGEA10
NM_021048.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.87

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High Hemizygotes in GnomAdExome4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAGEA10	NM_021048.5 linkuse as main transcript	c.689T>C	p.Ile230Thr	missense_variant	4/4	ENST00000370323.9	NP_066386.3	P43363B2RAE8
MAGEA10	NM_001011543.3 linkuse as main transcript	c.689T>C	p.Ile230Thr	missense_variant	5/5		NP_001011543.3	P43363B2RAE8
MAGEA10	NM_001251828.2 linkuse as main transcript	c.689T>C	p.Ile230Thr	missense_variant	5/5		NP_001238757.2	P43363B2RAE8
LOC100533997	NM_001204811.3 linkuse as main transcript	c.-278+3543T>C		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.689T>C	p.Ile230Thr	missense_variant	4/4	1	NM_021048.5	ENSP00000359347.4		P43363

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000545

AC:

AN:

183389

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

67825

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000721

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

AF:

0.0000100

AC:

AN:

1097591

Hom.:

Cov.:

AF XY:

0.00000826

AC XY:

AN XY:

363003

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000993

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000951

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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 09, 2022

The c.689T>C (p.I230T) alteration is located in exon 5 (coding exon 1) of the MAGEA10 gene. This alteration results from a T to C substitution at nucleotide position 689, causing the isoleucine (I) at amino acid position 230 to be replaced by a threonine (T). 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

Uncertain

0.42

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.34

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.051

T;T

FATHMM_MKL

Benign

0.080

LIST_S2

Benign

0.45

.;T

M_CAP

Benign

0.0083

MetaRNN

Uncertain

0.73

D;D

MetaSVM

Benign

-1.1

MutationAssessor

Pathogenic

3.1

M;M

PrimateAI

Uncertain

0.53

PROVEAN

Uncertain

-4.3

D;D

REVEL

Benign

0.20

Sift

Benign

0.093

T;T

Sift4G

Benign

0.12

T;T

Polyphen

0.89

P;P

Vest4

0.64

MutPred

0.67

Loss of stability (P = 0.0019);Loss of stability (P = 0.0019);

MVP

0.39

MPC

0.42

ClinPred

0.58

GERP RS

2.6

Varity_R

0.23

gMVP

0.82

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