ENST00000375695.2:c.190C>T

Variant names:

• chrX-51894771-C-T
• rs782185908
• ENST00000375695.2:c.190C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The ENST00000375695.2(MAGED1):​c.190C>T​(p.Pro64Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000875 in 1,142,624 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 0.000018 (0 hom., 1 hem., cov: 20)
  • Exomes 𝑓: 0.0000077 (0 hom. 1 hem.)
• Consequence: MAGED1 ENST00000375695.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.03
• 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 -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.09118655).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000375695.2. 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.46-282C>T		intron	N/A	NP_008917.3
	MAGED1	NM_001005333.2		c.190C>T	p.Pro64Ser	missense	Exon 3 of 14	NP_001005333.1	Q9Y5V3-2
	MAGED1	NM_001005332.2		c.46-282C>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.190C>T	p.Pro64Ser	missense	Exon 3 of 14	ENSP00000364847.2	Q9Y5V3-2
	MAGED1	ENST00000326587.12	TSL:1 MANE Select	c.46-282C>T		intron	N/A	ENSP00000325333.8	Q9Y5V3-1
	MAGED1	ENST00000898271.1		c.190C>T	p.Pro64Ser	missense	Exon 3 of 14	ENSP00000568330.1

Frequencies

GnomAD3 genomes AF: 0.0000184 AC: 2 AN: 108895 Hom.: 0 Cov.: 20

Gnomad AFR AF: 0.0000336

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: 0.0000191

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000777 AC: 1 AN: 128653 AF XY: 0.00

Gnomad AFR exome AF: 0.00

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: 0.0000161

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000774 AC: 8 AN: 1033729 Hom.: 0 Cov.: 32 AF XY: 0.00000301 AC XY: 1 AN XY: 332733

African (AFR) AF: 0.00 AC: 0 AN: 23694

American (AMR) AF: 0.00 AC: 0 AN: 21841

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15033

East Asian (EAS) AF: 0.00 AC: 0 AN: 29441

South Asian (SAS) AF: 0.00 AC: 0 AN: 43781

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38129

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3791

European-Non Finnish (NFE) AF: 0.00000982 AC: 8 AN: 814820

Other (OTH) AF: 0.00 AC: 0 AN: 43199

GnomAD4 genome AF: 0.0000184 AC: 2 AN: 108895 Hom.: 0 Cov.: 20 AF XY: 0.0000321 AC XY: 1 AN XY: 31185

African (AFR) AF: 0.0000336 AC: 1 AN: 29755

American (AMR) AF: 0.00 AC: 0 AN: 10349

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2621

East Asian (EAS) AF: 0.00 AC: 0 AN: 3405

South Asian (SAS) AF: 0.00 AC: 0 AN: 2348

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5758

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 236

European-Non Finnish (NFE) AF: 0.0000191 AC: 1 AN: 52282

Other (OTH) AF: 0.00 AC: 0 AN: 1471

Alfa AF: 0.000142 Hom.: 1

Bravo AF: 0.00000378

ExAC AF: 0.00000838 AC: 1

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	0.098
BayesDel_addAF	Benign	-0.52	T
BayesDel_noAF	Benign	-0.97
CADD	Benign	12
DANN	Benign	0.92
FATHMM_MKL	Benign	0.085	N
LIST_S2	Benign	0.41	T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.091	T
MetaSVM	Benign	-0.97	T
PhyloP100		1.0
PrimateAI	Benign	0.28	T
PROVEAN	Benign	0.22	N
REVEL	Benign	0.053
Sift	Benign	0.20	T
Sift4G	Benign	0.12	T
Polyphen		0.18	B
Vest4		0.34
MutPred		0.33		Gain of catalytic residue at P64 (P = 0.0016)
MVP		0.12
MPC		0.078
ClinPred		0.074	T
GERP RS		3.2
gMVP		0.18
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs782185908; hg19: chrX-51637867;