rs5951081

Variant names:

• chrX-51820684-T-C
• rs5951081
• NM_001005332.2:c.-37+17567T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001005332.2(MAGED1):​c.-37+17567T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0429 in 111,979 control chromosomes in the GnomAD database, including 120 homozygotes. There are 1,267 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 0.043 (120 hom., 1267 hem., cov: 22)
• Consequence: MAGED1 NM_001005332.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.207
• Publications: 1 publications found

Genes affected

MAGED1 (HGNC:6813): (MAGE family member D1) This gene is a member of the melanoma antigen gene (MAGE) family. Most of the genes of this family encode tumor specific antigens that are not expressed in normal adult tissues except testis. Although the protein encoded by this gene shares strong homology with members of the MAGE family, it is expressed in almost all normal adult tissues. This gene has been demonstrated to be involved in the p75 neurotrophin receptor mediated programmed cell death pathway. Three transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0704 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAGED1	NM_001005332.2	c.-37+17567T>C		intron_variant	Intron 1 of 12		NP_001005332.1
MAGED1	XM_011530835.3	c.-37+1276T>C		intron_variant	Intron 2 of 13		XP_011529137.1
MAGED1	XM_047442676.1	c.-30523+17567T>C		intron_variant	Intron 1 of 14		XP_047298632.1
MAGED1	XM_047442677.1	c.-111+17567T>C		intron_variant	Intron 1 of 13		XP_047298633.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAGED1	ENST00000375772.7	c.-37+17567T>C		intron_variant	Intron 1 of 12	5		ENSP00000364927.3

Frequencies

GnomAD3 genomes AF: 0.0429 AC: 4804 AN: 111928 Hom.: 119 Cov.: 22

Gnomad AFR AF: 0.00959

Gnomad AMI AF: 0.0352

Gnomad AMR AF: 0.0172

Gnomad ASJ AF: 0.0494

Gnomad EAS AF: 0.000555

Gnomad SAS AF: 0.0214

Gnomad FIN AF: 0.0364

Gnomad MID AF: 0.0126

Gnomad NFE AF: 0.0723

Gnomad OTH AF: 0.0332

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0429 AC: 4808 AN: 111979 Hom.: 120 Cov.: 22 AF XY: 0.0371 AC XY: 1267 AN XY: 34157

African (AFR) AF: 0.00957 AC: 296 AN: 30924

American (AMR) AF: 0.0172 AC: 181 AN: 10543

Ashkenazi Jewish (ASJ) AF: 0.0494 AC: 131 AN: 2653

East Asian (EAS) AF: 0.000557 AC: 2 AN: 3592

South Asian (SAS) AF: 0.0229 AC: 61 AN: 2658

European-Finnish (FIN) AF: 0.0364 AC: 221 AN: 6067

Middle Eastern (MID) AF: 0.00917 AC: 2 AN: 218

European-Non Finnish (NFE) AF: 0.0723 AC: 3840 AN: 53118

Other (OTH) AF: 0.0328 AC: 50 AN: 1525

Alfa AF: 0.0548 Hom.: 319

Bravo AF: 0.0390

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	6.3
DANN	Benign	0.94
PhyloP100		0.21
Mutation Taster		=100/0	polymorphism (auto)

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: rs5951081; hg19: chrX-51563780;