dbSNP rs377180452: MAGEA10:p.Ile134Arg (chrX-152135220-A-C) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_021048.5(MAGEA10):c.401T>G(p.Ile134Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000912 in 1,096,334 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. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I134T) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 22)

Exomes 𝑓: 9.1e-7 ( 0 hom. 0 hem. )

Consequence

MAGEA10
NM_021048.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.203

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 Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.37864143).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAGEA10	NM_021048.5 link	c.401T>G	p.Ile134Arg	missense_variant	Exon 4 of 4	ENST00000370323.9	NP_066386.3	P43363B2RAE8
MAGEA10	NM_001011543.3 link	c.401T>G	p.Ile134Arg	missense_variant	Exon 5 of 5		NP_001011543.3	P43363B2RAE8
MAGEA10	NM_001251828.2 link	c.401T>G	p.Ile134Arg	missense_variant	Exon 5 of 5		NP_001238757.2	P43363B2RAE8
LOC100533997	NM_001204811.3 link	c.-278+3255T>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.401T>G	p.Ile134Arg	missense_variant	Exon 4 of 4	1	NM_021048.5	ENSP00000359347.4		P43363

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

9.12e-7

AC:

AN:

1096334

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

361840

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:

0.00000119

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.46

CADD

Benign

DANN

Benign

0.69

DEOGEN2

Benign

0.18

T;T;T;T

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.10

.;T;T;T

M_CAP

Benign

0.011

MetaRNN

Benign

0.38

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.3

M;M;.;.

PrimateAI

Benign

0.47

PROVEAN

Pathogenic

-5.2

D;D;D;D

REVEL

Benign

0.10

Sift

Uncertain

0.0020

D;D;D;D

Sift4G

Pathogenic

0.0010

D;D;.;.

Polyphen

0.96

D;D;.;.

Vest4

0.48

MutPred

0.64

Gain of disorder (P = 0.0361);Gain of disorder (P = 0.0361);Gain of disorder (P = 0.0361);Gain of disorder (P = 0.0361);

MVP

0.22

MPC

0.32

ClinPred

0.79

GERP RS

1.4

Varity_R

0.72

gMVP

0.52

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over