NM_021048.5:c.1042A>G

Variant names:

• chrX-152134579-T-C
• rs751679256
• NM_021048.5:c.1042A>G

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_021048.5(MAGEA10):​c.1042A>G​(p.Thr348Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000191 in 1,204,623 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 4 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/21 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., 1 hem., cov: 21)
  • Exomes 𝑓: 0.000020 (0 hom. 3 hem.)
• Consequence: MAGEA10 NM_021048.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.47
• 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: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.04732099).
• BS2: High Hemizygotes in GnomAdExome4 at 3 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.1042A>G	p.Thr348Ala	missense	Exon 4 of 4	NP_066386.3	P43363
	MAGEA10	NM_001011543.3		c.1042A>G	p.Thr348Ala	missense	Exon 5 of 5	NP_001011543.3	P43363
	MAGEA10	NM_001251828.2		c.1042A>G	p.Thr348Ala	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.1042A>G	p.Thr348Ala	missense	Exon 4 of 4	ENSP00000359347.4	P43363
	MAGEA10	ENST00000244096.7	TSL:2	c.1042A>G	p.Thr348Ala	missense	Exon 5 of 5	ENSP00000244096.3	P43363
	ENSG00000266560	ENST00000509345.6	TSL:4	n.47+3896A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00000901 AC: 1 AN: 111007 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: 0.0000189

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000201 AC: 22 AN: 1093616 Hom.: 0 Cov.: 31 AF XY: 0.00000836 AC XY: 3 AN XY: 359044

African (AFR) AF: 0.00 AC: 0 AN: 26306

American (AMR) AF: 0.00 AC: 0 AN: 35201

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19360

East Asian (EAS) AF: 0.00 AC: 0 AN: 30193

South Asian (SAS) AF: 0.00 AC: 0 AN: 54034

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40525

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4123

European-Non Finnish (NFE) AF: 0.0000263 AC: 22 AN: 837923

Other (OTH) AF: 0.00 AC: 0 AN: 45951

GnomAD4 genome AF: 0.00000901 AC: 1 AN: 111007 Hom.: 0 Cov.: 21 AF XY: 0.0000301 AC XY: 1 AN XY: 33203

African (AFR) AF: 0.00 AC: 0 AN: 30434

American (AMR) AF: 0.00 AC: 0 AN: 10446

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2640

East Asian (EAS) AF: 0.00 AC: 0 AN: 3516

South Asian (SAS) AF: 0.00 AC: 0 AN: 2594

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5968

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 238

European-Non Finnish (NFE) AF: 0.0000189 AC: 1 AN: 53001

Other (OTH) AF: 0.00 AC: 0 AN: 1492

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.0000416

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000346 AC: 1

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	0.070
BayesDel_addAF	Benign	-0.59	T
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.16
DANN	Benign	0.81
DEOGEN2	Benign	0.010	T
FATHMM_MKL	Benign	0.0034	N
LIST_S2	Benign	0.096	T
M_CAP	Benign	0.0030	T
MetaRNN	Benign	0.047	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	1.4	L
PhyloP100		-1.5
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.97	N
REVEL	Benign	0.014
Sift	Benign	0.61	T
Sift4G	Benign	0.77	T
Polyphen		0.053	B
Vest4		0.042
MutPred		0.19		Gain of relative solvent accessibility (P = 0.0166)
MVP		0.34
MPC		0.097
ClinPred		0.022	T
GERP RS		-3.7
Varity_R		0.047
gMVP		0.11
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: rs751679256; hg19: chrX-151303051;