rs377536231

Variant names:

• chrX-51894745-C-T
• rs377536231
• ENST00000375695.2:c.164C>T

Variant summary

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

The NM_001005333.2(MAGED1):​c.164C>T​(p.Pro55Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000164 in 1,155,464 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 6 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000028 (0 hom., 0 hem., cov: 20)
  • Exomes 𝑓: 0.000015 (0 hom. 6 hem.)
• Consequence: MAGED1 NM_001005333.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.89
• 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 -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.078329384).
• BS2: High Hemizygotes in GnomAdExome4 at 6 gene

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.46-308C>T		intron	N/A	NP_008917.3
	MAGED1	NM_001005333.2		c.164C>T	p.Pro55Leu	missense	Exon 3 of 14	NP_001005333.1	Q9Y5V3-2
	MAGED1	NM_001005332.2		c.46-308C>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.164C>T	p.Pro55Leu	missense	Exon 3 of 14	ENSP00000364847.2	Q9Y5V3-2
	MAGED1	ENST00000326587.12	TSL:1 MANE Select	c.46-308C>T		intron	N/A	ENSP00000325333.8	Q9Y5V3-1
	MAGED1	ENST00000898271.1		c.164C>T	p.Pro55Leu	missense	Exon 3 of 14	ENSP00000568330.1

Frequencies

GnomAD3 genomes AF: 0.0000277 AC: 3 AN: 108130 Hom.: 0 Cov.: 20

Gnomad AFR AF: 0.000102

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: 0.0000226 AC: 3 AN: 132918 AF XY: 0.0000231

Gnomad AFR exome AF: 0.000163

Gnomad AMR exome AF: 0.0000637

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: 0.0000153 AC: 16 AN: 1047290 Hom.: 0 Cov.: 32 AF XY: 0.0000177 AC XY: 6 AN XY: 339552

African (AFR) AF: 0.000502 AC: 12 AN: 23882

American (AMR) AF: 0.0000440 AC: 1 AN: 22707

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15773

East Asian (EAS) AF: 0.00 AC: 0 AN: 29698

South Asian (SAS) AF: 0.00 AC: 0 AN: 45267

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38940

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3854

European-Non Finnish (NFE) AF: 0.00000121 AC: 1 AN: 823267

Other (OTH) AF: 0.0000456 AC: 2 AN: 43902

GnomAD4 genome AF: 0.0000277 AC: 3 AN: 108174 Hom.: 0 Cov.: 20 AF XY: 0.00 AC XY: 0 AN XY: 30540

African (AFR) AF: 0.000101 AC: 3 AN: 29573

American (AMR) AF: 0.00 AC: 0 AN: 10319

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2611

East Asian (EAS) AF: 0.00 AC: 0 AN: 3362

South Asian (SAS) AF: 0.00 AC: 0 AN: 2285

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5728

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 214

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 51954

Other (OTH) AF: 0.00 AC: 0 AN: 1465

Alfa AF: 0.000142 Hom.: 1

Bravo AF: 0.0000604

ESP6500AA AF: 0.000261 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000332 AC: 4

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	0.16
BayesDel_addAF	Benign	-0.64	T
BayesDel_noAF	Benign	-0.86
CADD	Benign	8.9
DANN	Uncertain	0.98
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.53	T
M_CAP	Benign	0.062	D
MetaRNN	Benign	0.078	T
MetaSVM	Benign	-1.0	T
PhyloP100		1.9
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.45	N
REVEL	Benign	0.046
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.28	T
Polyphen		0.025	B
Vest4		0.25
MVP		0.11
MPC		0.079
ClinPred		0.16	T
GERP RS		3.2
gMVP		0.14
Mutation Taster		=99/1	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: rs377536231; hg19: chrX-51637841;