rs371038613

Variant names:

• chrX-51894787-C-A
• ENST00000375695.2:c.206C>A

Your query was ambiguous. Multiple possible variants found:

• chrX-51894787-C-A
• chrX-51894787-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001005333.2(MAGED1):​c.206C>A​(p.Pro69Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000969 in 1,031,651 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. 12/17 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 20)
  • Exomes 𝑓: 9.7e-7 (0 hom. 1 hem.)
• Consequence: MAGED1 NM_001005333.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.534

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06078756).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAGED1	NM_006986.4	c.46-266C>A		intron_variant	Intron 2 of 12	ENST00000326587.12	NP_008917.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAGED1	ENST00000326587.12	c.46-266C>A		intron_variant	Intron 2 of 12	1	NM_006986.4	ENSP00000325333.8

Frequencies

GnomAD3 genomes Cov.: 20

GnomAD4 exome AF: 9.69e-7 AC: 1 AN: 1031651 Hom.: 0 Cov.: 32 AF XY: 0.00000301 AC XY: 1 AN XY: 332723

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000123

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 20

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.57	T
BayesDel_noAF	Benign	-1.1
CADD	Benign	1.5
DANN	Benign	0.60
FATHMM_MKL	Benign	0.025	N
LIST_S2	Benign	0.33	T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.061	T
MetaSVM	Benign	-1.1	T
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.12	N
REVEL	Benign	0.046
Sift	Benign	0.28	T
Sift4G	Uncertain	0.025	D
Polyphen		0.10	B
Vest4		0.15
MutPred		0.14		Loss of glycosylation at P69 (P = 0.0207);
MVP		0.082
MPC		0.072
ClinPred		0.068	T
GERP RS		-1.9
gMVP		0.14

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-51637883;