rs141749849

Variant names:

• chrX-51894706-C-T
• rs141749849
• ENST00000375695.2:c.125C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001005333.2(MAGED1):​c.125C>T​(p.Thr42Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,168,340 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000019 (0 hom., 1 hem., cov: 19)
  • Exomes 𝑓: 0.0000019 (0 hom. 1 hem.)
• Consequence: MAGED1 NM_001005333.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.867
• 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.053423107).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001005333.2. 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.46-347C>T		intron	N/A	NP_008917.3
	MAGED1	NM_001005333.2		c.125C>T	p.Thr42Ile	missense	Exon 3 of 14	NP_001005333.1	Q9Y5V3-2
	MAGED1	NM_001005332.2		c.46-347C>T		intron	N/A	NP_001005332.1	Q9Y5V3-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAGED1	ENST00000375695.2	TSL:1	c.125C>T	p.Thr42Ile	missense	Exon 3 of 14	ENSP00000364847.2	Q9Y5V3-2
	MAGED1	ENST00000326587.12	TSL:1 MANE Select	c.46-347C>T		intron	N/A	ENSP00000325333.8	Q9Y5V3-1
	MAGED1	ENST00000898271.1		c.125C>T	p.Thr42Ile	missense	Exon 3 of 14	ENSP00000568330.1

Frequencies

GnomAD3 genomes AF: 0.0000187 AC: 2 AN: 106769 Hom.: 0 Cov.: 19

Gnomad AFR AF: 0.0000687

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: 0.00000669 AC: 1 AN: 149388 AF XY: 0.00

Gnomad AFR exome AF: 0.0000801

Gnomad AMR exome AF: 0.00

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: 0.00000188 AC: 2 AN: 1061571 Hom.: 0 Cov.: 32 AF XY: 0.00000292 AC XY: 1 AN XY: 342583

African (AFR) AF: 0.0000830 AC: 2 AN: 24104

American (AMR) AF: 0.00 AC: 0 AN: 25574

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17561

East Asian (EAS) AF: 0.00 AC: 0 AN: 29918

South Asian (SAS) AF: 0.00 AC: 0 AN: 48407

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39990

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3950

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 827563

Other (OTH) AF: 0.00 AC: 0 AN: 44504

GnomAD4 genome AF: 0.0000187 AC: 2 AN: 106769 Hom.: 0 Cov.: 19 AF XY: 0.0000342 AC XY: 1 AN XY: 29251

African (AFR) AF: 0.0000687 AC: 2 AN: 29107

American (AMR) AF: 0.00 AC: 0 AN: 10086

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2584

East Asian (EAS) AF: 0.00 AC: 0 AN: 3357

South Asian (SAS) AF: 0.00 AC: 0 AN: 2233

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5528

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 235

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 51559

Other (OTH) AF: 0.00 AC: 0 AN: 1424

Alfa AF: 0.00 Hom.: 0

ESP6500AA AF: 0.000261 AC: 1

ESP6500EA AF: 0.00 AC: 0

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	0.19
BayesDel_addAF	Benign	-0.75	T
BayesDel_noAF	Benign	-1.1
CADD	Benign	6.4
DANN	Benign	0.27
FATHMM_MKL	Benign	0.043	N
LIST_S2	Benign	0.36	T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.053	T
MetaSVM	Benign	-0.92	T
PhyloP100		-0.87
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-0.25	N
REVEL	Benign	0.010
Sift	Benign	0.36	T
Sift4G	Uncertain	0.034	D
Polyphen		0.11	B
Vest4		0.11
MVP		0.21
MPC		0.083
ClinPred		0.014	T
GERP RS		1.6
gMVP		0.17
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: rs141749849; hg19: chrX-51637802;