X-51895693-C-T

Variant names:

• chrX-51895693-C-T
• rs372248500
• NM_006986.4:c.686C>T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_006986.4(MAGED1):​c.686C>T​(p.Ser229Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000208 in 1,201,066 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 8 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: 𝑓 0.00017 (0 hom., 7 hem., cov: 24)
  • Exomes 𝑓: 0.0000055 (0 hom. 1 hem.)
• Consequence: MAGED1 NM_006986.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.59
• 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.11486143).
• BS2: High Hemizygotes in GnomAd4 at 7 gene

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.686C>T	p.Ser229Leu	missense	Exon 3 of 13	NP_008917.3
	MAGED1	NM_001005333.2		c.854C>T	p.Ser285Leu	missense	Exon 4 of 14	NP_001005333.1	Q9Y5V3-2
	MAGED1	NM_001005332.2		c.686C>T	p.Ser229Leu	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.686C>T	p.Ser229Leu	missense	Exon 3 of 13	ENSP00000325333.8	Q9Y5V3-1
	MAGED1	ENST00000375695.2	TSL:1	c.854C>T	p.Ser285Leu	missense	Exon 4 of 14	ENSP00000364847.2	Q9Y5V3-2
	MAGED1	ENST00000898271.1		c.854C>T	p.Ser285Leu	missense	Exon 4 of 14	ENSP00000568330.1

Frequencies

GnomAD3 genomes AF: 0.000169 AC: 19 AN: 112357 Hom.: 0 Cov.: 24

Gnomad AFR AF: 0.000615

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000372 AC: 6 AN: 161451 AF XY: 0.00

Gnomad AFR exome AF: 0.000267

Gnomad AMR exome AF: 0.000117

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000551 AC: 6 AN: 1088709 Hom.: 0 Cov.: 32 AF XY: 0.00000281 AC XY: 1 AN XY: 355785

African (AFR) AF: 0.0000381 AC: 1 AN: 26279

American (AMR) AF: 0.000117 AC: 4 AN: 34059

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19199

East Asian (EAS) AF: 0.00 AC: 0 AN: 29924

South Asian (SAS) AF: 0.00 AC: 0 AN: 52261

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39898

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 837157

Other (OTH) AF: 0.0000218 AC: 1 AN: 45809

GnomAD4 genome AF: 0.000169 AC: 19 AN: 112357 Hom.: 0 Cov.: 24 AF XY: 0.000203 AC XY: 7 AN XY: 34519

African (AFR) AF: 0.000615 AC: 19 AN: 30897

American (AMR) AF: 0.00 AC: 0 AN: 10652

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2648

East Asian (EAS) AF: 0.00 AC: 0 AN: 3574

South Asian (SAS) AF: 0.00 AC: 0 AN: 2699

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6168

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 239

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 53280

Other (OTH) AF: 0.00 AC: 0 AN: 1515

Alfa AF: 0.000274 Hom.: 2

Bravo AF: 0.000166

ESP6500AA AF: 0.000261 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000829 AC: 10

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	0.090
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.47
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.15	T
FATHMM_MKL	Benign	0.64	D
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.81	L
PhyloP100		1.6
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.069
Sift	Uncertain	0.0010	D
Sift4G	Benign	0.36	T
Polyphen		0.99	D
Vest4		0.19
MVP		0.33
MPC		0.069
ClinPred		0.11	T
GERP RS		4.2
Varity_R		0.24
gMVP		0.46
Mutation Taster		=98/2	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: rs372248500; hg19: chrX-51638789;