NM_021048.5:c.866G>C

Variant names:

• chrX-152134755-C-G
• rs371673293
• NM_021048.5:c.866G>C

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_021048.5(MAGEA10):​c.866G>C​(p.Ser289Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000752 in 1,209,627 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 25 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/21 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., 0 hem., cov: 21)
  • Exomes 𝑓: 0.000082 (0 hom. 25 hem.)
• Consequence: MAGEA10 NM_021048.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.417
• Publications: 0 publications found

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]

LOC100533997 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.20797586).
• BS2: High Hemizygotes in GnomAdExome4 at 25 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021048.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAGEA10	NM_021048.5	MANE Select	c.866G>C	p.Ser289Thr	missense	Exon 4 of 4	NP_066386.3	P43363
	MAGEA10	NM_001011543.3		c.866G>C	p.Ser289Thr	missense	Exon 5 of 5	NP_001011543.3	P43363
	MAGEA10	NM_001251828.2		c.866G>C	p.Ser289Thr	missense	Exon 5 of 5	NP_001238757.2	P43363

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAGEA10	ENST00000370323.9	TSL:1 MANE Select	c.866G>C	p.Ser289Thr	missense	Exon 4 of 4	ENSP00000359347.4	P43363
	MAGEA10	ENST00000244096.7	TSL:2	c.866G>C	p.Ser289Thr	missense	Exon 5 of 5	ENSP00000244096.3	P43363
	ENSG00000266560	ENST00000509345.6	TSL:4	n.47+3720G>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00000898 AC: 1 AN: 111417 Hom.: 0 Cov.: 21

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: 0.0000188

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000218 AC: 4 AN: 183519 AF XY: 0.0000147

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000488

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000820 AC: 90 AN: 1098210 Hom.: 0 Cov.: 33 AF XY: 0.0000688 AC XY: 25 AN XY: 363564

African (AFR) AF: 0.00 AC: 0 AN: 26403

American (AMR) AF: 0.00 AC: 0 AN: 35207

Ashkenazi Jewish (ASJ) AF: 0.0000516 AC: 1 AN: 19386

East Asian (EAS) AF: 0.00 AC: 0 AN: 30206

South Asian (SAS) AF: 0.00 AC: 0 AN: 54145

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40533

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4136

European-Non Finnish (NFE) AF: 0.0000986 AC: 83 AN: 842100

Other (OTH) AF: 0.000130 AC: 6 AN: 46094

GnomAD4 genome AF: 0.00000898 AC: 1 AN: 111417 Hom.: 0 Cov.: 21 AF XY: 0.00 AC XY: 0 AN XY: 33579

African (AFR) AF: 0.00 AC: 0 AN: 30617

American (AMR) AF: 0.00 AC: 0 AN: 10554

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2633

East Asian (EAS) AF: 0.00 AC: 0 AN: 3520

South Asian (SAS) AF: 0.00 AC: 0 AN: 2584

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6002

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 237

European-Non Finnish (NFE) AF: 0.0000188 AC: 1 AN: 53076

Other (OTH) AF: 0.00 AC: 0 AN: 1506

Alfa AF: 0.0000434 Hom.: 0

Bravo AF: 0.0000227

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000297 AC: 2

ExAC AF: 0.0000165 AC: 2

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.46	T
BayesDel_noAF	Benign	-0.84
CADD	Benign	16
DANN	Uncertain	0.98
DEOGEN2	Benign	0.11	T
FATHMM_MKL	Benign	0.043	N
LIST_S2	Benign	0.60	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.9	L
PhyloP100		0.42
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.14
Sift	Benign	0.22	T
Sift4G	Benign	0.064	T
Polyphen		0.99	D
Vest4		0.12
MVP		0.22
MPC		0.42
ClinPred		0.42	T
GERP RS		2.6
Varity_R		0.31
gMVP		0.43
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs371673293; hg19: chrX-151303227;