X-51894750-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The ENST00000375695.2(MAGED1):c.169G>A(p.Val57Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000739 in 1,146,554 control chromosomes in the GnomAD database, including 3 homozygotes. There are 197 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 11/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0039 (1 hom., 79 hem., cov: 20)
  • Exomes 𝑓: 0.00043 (2 hom. 118 hem.)
• Consequence: MAGED1 ENST00000375695.2 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.662

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

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0034484267).
• BP6: Variant X-51894750-G-A is Benign according to our data. Variant chrX-51894750-G-A is described in ClinVar as [Benign]. Clinvar id is 790239.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-51894750-G-A is described in Lovd as [Likely_benign].
• BS2: High Hemizygotes in GnomAd at 79 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAGED1	NM_006986.4	c.46-303G>A		intron_variant		ENST00000326587.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAGED1	ENST00000326587.12	c.46-303G>A		intron_variant		1	NM_006986.4	P2

Frequencies

GnomAD3 genomes AF: 0.00386 AC: 401 AN: 103852 Hom.: 1 Cov.: 20 AF XY: 0.00284 AC XY: 79 AN XY: 27840

Gnomad AFR AF: 0.0139

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00125

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: 0.0000390

Gnomad OTH AF: 0.00216

GnomAD3 exomes AF: 0.00171 AC: 224 AN: 131293 Hom.: 2 AF XY: 0.000999 AC XY: 43 AN XY: 43023

Gnomad AFR exome AF: 0.0170

Gnomad AMR exome AF: 0.000644

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000102

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000158

Gnomad OTH exome AF: 0.00101

GnomAD4 exome AF: 0.000428 AC: 446 AN: 1042686 Hom.: 2 Cov.: 32 AF XY: 0.000351 AC XY: 118 AN XY: 336590

Gnomad4 AFR exome AF: 0.0157

Gnomad4 AMR exome AF: 0.000626

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000225

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000853

Gnomad4 OTH exome AF: 0.00105

GnomAD4 genome AF: 0.00386 AC: 401 AN: 103868 Hom.: 1 Cov.: 20 AF XY: 0.00283 AC XY: 79 AN XY: 27866

Gnomad4 AFR AF: 0.0139

Gnomad4 AMR AF: 0.00125

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000390

Gnomad4 OTH AF: 0.00213

Alfa AF: 0.000443 Hom.: 11

ESP6500AA AF: 0.0169 AC: 65

ESP6500EA AF: 0.000297 AC: 2

ExAC AF: 0.00153 AC: 184

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.98	T
BayesDel_noAF	Benign	-1.2
Cadd	Benign	2.4
Dann	Benign	0.86
FATHMM_MKL	Benign	0.024	N
LIST_S2	Benign	0.35	T
MetaRNN	Benign	0.0034	T
MetaSVM	Benign	-0.91	T
MutationTaster	Benign	1.0	N;N;N;N
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.21	N
REVEL	Benign	0.015
Sift	Benign	0.096	T
Sift4G	Benign	0.39	T
Polyphen		0.0	B
Vest4		0.030
MVP		0.11
MPC		0.064
ClinPred		0.00022	T
GERP RS		-4.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
gMVP		0.057

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

Publications

LitVar

Other links and lift over

dbSNP: rs145588024; hg19: chrX-51637846; COSMIC: COSV100431736; COSMIC: COSV100431736;