rs781919008

Variant names:

• chrX-51895605-G-A
• rs781919008
• NM_006986.4:c.598G>A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_006986.4(MAGED1):​c.598G>A​(p.Val200Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000132 in 1,210,295 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 5 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000018 (0 hom., 0 hem., cov: 23)
  • Exomes 𝑓: 0.000013 (0 hom. 5 hem.)
• Consequence: MAGED1 NM_006986.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.530
• 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: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.022335917).
• BS2: High Hemizygotes in GnomAdExome4 at 5 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.598G>A	p.Val200Ile	missense	Exon 3 of 13	NP_008917.3
	MAGED1	NM_001005333.2		c.766G>A	p.Val256Ile	missense	Exon 4 of 14	NP_001005333.1	Q9Y5V3-2
	MAGED1	NM_001005332.2		c.598G>A	p.Val200Ile	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.598G>A	p.Val200Ile	missense	Exon 3 of 13	ENSP00000325333.8	Q9Y5V3-1
	MAGED1	ENST00000375695.2	TSL:1	c.766G>A	p.Val256Ile	missense	Exon 4 of 14	ENSP00000364847.2	Q9Y5V3-2
	MAGED1	ENST00000898271.1		c.766G>A	p.Val256Ile	missense	Exon 4 of 14	ENSP00000568330.1

Frequencies

GnomAD3 genomes AF: 0.0000178 AC: 2 AN: 112346 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000187

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: 0.0000713 AC: 13 AN: 182432 AF XY: 0.0000747

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000475

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: 0.0000128 AC: 14 AN: 1097949 Hom.: 0 Cov.: 32 AF XY: 0.0000138 AC XY: 5 AN XY: 363309

African (AFR) AF: 0.00 AC: 0 AN: 26401

American (AMR) AF: 0.000398 AC: 14 AN: 35194

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19377

East Asian (EAS) AF: 0.00 AC: 0 AN: 30205

South Asian (SAS) AF: 0.00 AC: 0 AN: 53965

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40523

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 842054

Other (OTH) AF: 0.00 AC: 0 AN: 46094

GnomAD4 genome AF: 0.0000178 AC: 2 AN: 112346 Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0 AN XY: 34502

African (AFR) AF: 0.00 AC: 0 AN: 30889

American (AMR) AF: 0.000187 AC: 2 AN: 10673

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2651

East Asian (EAS) AF: 0.00 AC: 0 AN: 3568

South Asian (SAS) AF: 0.00 AC: 0 AN: 2707

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6167

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 238

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 53260

Other (OTH) AF: 0.00 AC: 0 AN: 1509

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000453

ExAC AF: 0.0000659 AC: 8

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	0.065
BayesDel_addAF	Benign	-0.66	T
BayesDel_noAF	Benign	-0.86
CADD	Benign	8.1
DANN	Benign	0.81
DEOGEN2	Benign	0.16	T
FATHMM_MKL	Benign	0.51	D
LIST_S2	Benign	0.59	T
M_CAP	Benign	0.0061	T
MetaRNN	Benign	0.022	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.0	L
PhyloP100		0.53
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.41	N
REVEL	Benign	0.035
Sift	Benign	0.088	T
Sift4G	Benign	0.38	T
Polyphen		0.13	B
Vest4		0.065
MutPred		0.17		Loss of phosphorylation at T197 (P = 0.0993)
MVP		0.23
MPC		0.064
ClinPred		0.056	T
GERP RS		0.080
Varity_R		0.049
gMVP		0.55
Mutation Taster		=100/0	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: rs781919008; hg19: chrX-51638701;