chrX-51895136-C-G

Variant names:

• chrX-51895136-C-G
• rs1928674730
• NM_006986.4:c.129C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006986.4(MAGED1):​c.129C>G​(p.Asn43Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000729 in 1,098,033 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. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.0000073 (0 hom. 1 hem.)
• Consequence: MAGED1 NM_006986.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.85
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22102025).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006986.4. 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
	MAGED1	NM_006986.4	MANE Select	c.129C>G	p.Asn43Lys	missense	Exon 3 of 13	NP_008917.3
	MAGED1	NM_001005333.2		c.297C>G	p.Asn99Lys	missense	Exon 4 of 14	NP_001005333.1	Q9Y5V3-2
	MAGED1	NM_001005332.2		c.129C>G	p.Asn43Lys	missense	Exon 3 of 13	NP_001005332.1	Q9Y5V3-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAGED1	ENST00000326587.12	TSL:1 MANE Select	c.129C>G	p.Asn43Lys	missense	Exon 3 of 13	ENSP00000325333.8	Q9Y5V3-1
	MAGED1	ENST00000375695.2	TSL:1	c.297C>G	p.Asn99Lys	missense	Exon 4 of 14	ENSP00000364847.2	Q9Y5V3-2
	MAGED1	ENST00000898271.1		c.297C>G	p.Asn99Lys	missense	Exon 4 of 14	ENSP00000568330.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 0.00000729 AC: 8 AN: 1098033 Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 1 AN XY: 363387

African (AFR) AF: 0.00 AC: 0 AN: 26398

American (AMR) AF: 0.00 AC: 0 AN: 35204

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19382

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 54108

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40522

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4136

European-Non Finnish (NFE) AF: 0.00000950 AC: 8 AN: 841989

Other (OTH) AF: 0.00 AC: 0 AN: 46092

GnomAD4 genome Cov.: 23

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

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	0.26
BayesDel_addAF	Benign	-0.43	T
BayesDel_noAF	Benign	-0.86
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.12	T
FATHMM_MKL	Benign	0.68	D
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.34	N
PhyloP100		2.8
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-0.57	N
REVEL	Benign	0.068
Sift	Uncertain	0.0030	D
Sift4G	Benign	0.79	T
Polyphen		0.95	P
Vest4		0.15
MutPred		0.21		Gain of ubiquitination at N43 (P = 0.0069)
MVP		0.59
MPC		0.088
ClinPred		0.52	D
GERP RS		3.9
Varity_R		0.29
gMVP		0.18
Mutation Taster		=96/4	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: rs1928674730; hg19: chrX-51638232;