X-153183202-C-T

Variant names:

• chrX-153183202-C-T
• rs2233045
• NM_004988.5:c.813C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_004988.5(MAGEA1):​c.813C>T​(p.Leu271Leu) 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
• Publications: 12 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004988.5. 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
	MAGEA1	NM_004988.5	MANE Select	c.813C>T	p.Leu271Leu	synonymous	Exon 3 of 3	NP_004979.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAGEA1	ENST00000356661.7	TSL:1 MANE Select	c.813C>T	p.Leu271Leu	synonymous	Exon 3 of 3	ENSP00000349085.5	P43355

Frequencies

GnomAD3 genomes AF: 0.112 AC: 12514 AN: 112126 Hom.: 572 Cov.: 24

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

GnomAD2 exomes AF: 0.132 AC: 24220 AN: 183466 AF XY: 0.142

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 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

African (AFR) AF: 0.0463 AC: 1222 AN: 26401

American (AMR) AF: 0.0644 AC: 2268 AN: 35204

Ashkenazi Jewish (ASJ) AF: 0.168 AC: 3248 AN: 19383

East Asian (EAS) AF: 0.185 AC: 5584 AN: 30206

South Asian (SAS) AF: 0.201 AC: 10866 AN: 54143

European-Finnish (FIN) AF: 0.152 AC: 6168 AN: 40529

Middle Eastern (MID) AF: 0.125 AC: 518 AN: 4136

European-Non Finnish (NFE) AF: 0.134 AC: 112794 AN: 842061

Other (OTH) AF: 0.138 AC: 6371 AN: 46096

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

African (AFR) AF: 0.0425 AC: 1316 AN: 30986

American (AMR) AF: 0.0954 AC: 1019 AN: 10685

Ashkenazi Jewish (ASJ) AF: 0.174 AC: 461 AN: 2649

East Asian (EAS) AF: 0.173 AC: 609 AN: 3530

South Asian (SAS) AF: 0.191 AC: 515 AN: 2692

European-Finnish (FIN) AF: 0.140 AC: 848 AN: 6077

Middle Eastern (MID) AF: 0.106 AC: 23 AN: 216

European-Non Finnish (NFE) AF: 0.142 AC: 7524 AN: 53127

Other (OTH) AF: 0.112 AC: 172 AN: 1536

Alfa AF: 0.132 Hom.: 1153

Bravo AF: 0.103

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.023
DANN	Benign	0.74
PhyloP100		-1.2

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