rs2233045

Positions:

• chrX-153183202-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_004988.5(MAGEA1):​c.813C>T​(p.Leu271=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.133 in 1,210,339 control chromosomes in the GnomAD database, including 7,592 homozygotes. There are 54,501 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.11 (572 hom., 3814 hem., cov: 24)
  • Exomes 𝑓: 0.14 (7020 hom. 50687 hem.)
• Consequence: MAGEA1 NM_004988.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.16

Genes affected

MAGEA1 (HGNC:6796): (MAGE family member A1) 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. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP7: Synonymous conserved (PhyloP=-1.16 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.178 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAGEA1	NM_004988.5	c.813C>T	p.Leu271=	synonymous_variant	3/3	ENST00000356661.7	NP_004979.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAGEA1	ENST00000356661.7	c.813C>T	p.Leu271=	synonymous_variant	3/3	1	NM_004988.5	ENSP00000349085	P1

Frequencies

GnomAD3 genomes AF: 0.112 AC: 12514 AN: 112126 Hom.: 572 Cov.: 24 AF XY: 0.111 AC XY: 3810 AN XY: 34280

Gnomad AFR AF: 0.0425

Gnomad AMI AF: 0.0396

Gnomad AMR AF: 0.0957

Gnomad ASJ AF: 0.174

Gnomad EAS AF: 0.172

Gnomad SAS AF: 0.190

Gnomad FIN AF: 0.140

Gnomad MID AF: 0.105

Gnomad NFE AF: 0.142

Gnomad OTH AF: 0.113

GnomAD3 exomes AF: 0.132 AC: 24220 AN: 183466 Hom.: 1110 AF XY: 0.142 AC XY: 9651 AN XY: 67900

Gnomad AFR exome AF: 0.0455

Gnomad AMR exome AF: 0.0615

Gnomad ASJ exome AF: 0.165

Gnomad EAS exome AF: 0.178

Gnomad SAS exome AF: 0.197

Gnomad FIN exome AF: 0.156

Gnomad NFE exome AF: 0.139

Gnomad OTH exome AF: 0.133

GnomAD4 exome AF: 0.136 AC: 149039 AN: 1098159 Hom.: 7020 Cov.: 33 AF XY: 0.139 AC XY: 50687 AN XY: 363525

Gnomad4 AFR exome AF: 0.0463

Gnomad4 AMR exome AF: 0.0644

Gnomad4 ASJ exome AF: 0.168

Gnomad4 EAS exome AF: 0.185

Gnomad4 SAS exome AF: 0.201

Gnomad4 FIN exome AF: 0.152

Gnomad4 NFE exome AF: 0.134

Gnomad4 OTH exome AF: 0.138

GnomAD4 genome AF: 0.112 AC: 12514 AN: 112180 Hom.: 572 Cov.: 24 AF XY: 0.111 AC XY: 3814 AN XY: 34344

Gnomad4 AFR AF: 0.0425

Gnomad4 AMR AF: 0.0954

Gnomad4 ASJ AF: 0.174

Gnomad4 EAS AF: 0.173

Gnomad4 SAS AF: 0.191

Gnomad4 FIN AF: 0.140

Gnomad4 NFE AF: 0.142

Gnomad4 OTH AF: 0.112

Alfa AF: 0.132 Hom.: 1153

Bravo AF: 0.103

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.023
DANN	Benign	0.74

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

Other links and lift over

dbSNP: rs2233045; hg19: chrX-152482198; COSMIC: COSV63118574;