X-152135337-G-A

Variant names:

• chrX-152135337-G-A
• rs748262488
• NM_021048.5:c.284C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_021048.5(MAGEA10):​c.284C>T​(p.Ser95Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000414 in 1,208,496 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/21 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: 22)
  • Exomes 𝑓: 0.0000036 (0 hom. 1 hem.)
• Consequence: MAGEA10 NM_021048.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.15
• 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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04347253).

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.284C>T	p.Ser95Leu	missense	Exon 4 of 4	NP_066386.3	P43363
	MAGEA10	NM_001011543.3		c.284C>T	p.Ser95Leu	missense	Exon 5 of 5	NP_001011543.3	P43363
	MAGEA10	NM_001251828.2		c.284C>T	p.Ser95Leu	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.284C>T	p.Ser95Leu	missense	Exon 4 of 4	ENSP00000359347.4	P43363
	MAGEA10	ENST00000244096.7	TSL:2	c.284C>T	p.Ser95Leu	missense	Exon 5 of 5	ENSP00000244096.3	P43363
	MAGEA10	ENST00000444834.6	TSL:3	c.284C>T	p.Ser95Leu	missense	Exon 5 of 5	ENSP00000406161.2	C9J958

Frequencies

GnomAD3 genomes AF: 0.00000900 AC: 1 AN: 111132 Hom.: 0 Cov.: 22

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

GnomAD2 exomes AF: 0.0000330 AC: 6 AN: 181651 AF XY: 0.0000453

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000367

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000494

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000365 AC: 4 AN: 1097313 Hom.: 0 Cov.: 33 AF XY: 0.00000276 AC XY: 1 AN XY: 362715

African (AFR) AF: 0.00 AC: 0 AN: 26387

American (AMR) AF: 0.0000285 AC: 1 AN: 35123

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19317

East Asian (EAS) AF: 0.00 AC: 0 AN: 30202

South Asian (SAS) AF: 0.00 AC: 0 AN: 53913

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40454

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4129

European-Non Finnish (NFE) AF: 0.00000356 AC: 3 AN: 841742

Other (OTH) AF: 0.00 AC: 0 AN: 46046

GnomAD4 genome AF: 0.00000899 AC: 1 AN: 111183 Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0 AN XY: 33357

African (AFR) AF: 0.00 AC: 0 AN: 30579

American (AMR) AF: 0.00 AC: 0 AN: 10481

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2635

East Asian (EAS) AF: 0.00 AC: 0 AN: 3508

South Asian (SAS) AF: 0.00 AC: 0 AN: 2570

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6030

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 219

European-Non Finnish (NFE) AF: 0.0000189 AC: 1 AN: 52969

Other (OTH) AF: 0.00 AC: 0 AN: 1508

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ExAC AF: 0.0000577 AC: 7

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	0.082
BayesDel_addAF	Benign	-0.51	T
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.5
DANN	Benign	0.59
DEOGEN2	Benign	0.025	T
FATHMM_MKL	Benign	0.035	N
LIST_S2	Benign	0.20	T
M_CAP	Benign	0.0067	T
MetaRNN	Benign	0.043	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		-1.2
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.040
Sift	Benign	0.040	D
Sift4G	Benign	0.064	T
Polyphen		0.15	B
Vest4		0.020
MutPred		0.23		Loss of phosphorylation at S95 (P = 0.0187)
MVP		0.11
MPC		0.083
ClinPred		0.073	T
GERP RS		-0.96
Varity_R		0.058
gMVP		0.13
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs748262488; hg19: chrX-151303809; COSMIC: COSV99726548; COSMIC: COSV99726548;