ENST00000375695.2:c.206C>T

Variant names:

• chrX-51894787-C-T
• rs371038613
• ENST00000375695.2:c.206C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The ENST00000375695.2(MAGED1):​c.206C>T​(p.Pro69Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000133 in 1,140,816 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 50 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 Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000092 (0 hom., 2 hem., cov: 20)
  • Exomes 𝑓: 0.00014 (0 hom. 48 hem.)
• Consequence: MAGED1 ENST00000375695.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.534
• 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: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.042477876).
• BP6: Variant X-51894787-C-T is Benign according to our data. Variant chrX-51894787-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2321805.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Hemizygotes in GnomAd4 at 2 gene

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.46-266C>T		intron	N/A	NP_008917.3
	MAGED1	NM_001005333.2		c.206C>T	p.Pro69Leu	missense	Exon 3 of 14	NP_001005333.1	Q9Y5V3-2
	MAGED1	NM_001005332.2		c.46-266C>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.206C>T	p.Pro69Leu	missense	Exon 3 of 14	ENSP00000364847.2	Q9Y5V3-2
	MAGED1	ENST00000326587.12	TSL:1 MANE Select	c.46-266C>T		intron	N/A	ENSP00000325333.8	Q9Y5V3-1
	MAGED1	ENST00000898271.1		c.206C>T	p.Pro69Leu	missense	Exon 3 of 14	ENSP00000568330.1

Frequencies

GnomAD3 genomes AF: 0.0000916 AC: 10 AN: 109165 Hom.: 0 Cov.: 20

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000289

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: 0.000114

Gnomad OTH AF: 0.000682

GnomAD2 exomes AF: 0.0000236 AC: 3 AN: 126862 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: 0.0000488

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000138 AC: 142 AN: 1031651 Hom.: 0 Cov.: 32 AF XY: 0.000144 AC XY: 48 AN XY: 332723

African (AFR) AF: 0.00 AC: 0 AN: 23657

American (AMR) AF: 0.00 AC: 0 AN: 21670

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14865

East Asian (EAS) AF: 0.0000340 AC: 1 AN: 29431

South Asian (SAS) AF: 0.00 AC: 0 AN: 43512

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37941

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3744

European-Non Finnish (NFE) AF: 0.000170 AC: 138 AN: 813723

Other (OTH) AF: 0.0000696 AC: 3 AN: 43108

GnomAD4 genome AF: 0.0000916 AC: 10 AN: 109165 Hom.: 0 Cov.: 20 AF XY: 0.0000636 AC XY: 2 AN XY: 31453

African (AFR) AF: 0.00 AC: 0 AN: 29844

American (AMR) AF: 0.000289 AC: 3 AN: 10382

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2624

East Asian (EAS) AF: 0.00 AC: 0 AN: 3400

South Asian (SAS) AF: 0.00 AC: 0 AN: 2384

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5735

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

European-Non Finnish (NFE) AF: 0.000114 AC: 6 AN: 52419

Other (OTH) AF: 0.000682 AC: 1 AN: 1466

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000945

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000149 AC: 1

ExAC AF: 0.0000254 AC: 3

ClinVar

ClinVar submissions

Significance: Likely benign

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	0.12
BayesDel_addAF	Benign	-0.72	T
BayesDel_noAF	Benign	-1.1
CADD	Benign	1.8
DANN	Benign	0.63
FATHMM_MKL	Benign	0.0060	N
LIST_S2	Benign	0.41	T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.042	T
MetaSVM	Benign	-0.98	T
PhyloP100		-0.53
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.56	N
REVEL	Benign	0.023
Sift	Benign	1.0	T
Sift4G	Uncertain	0.019	D
Polyphen		0.0	B
Vest4		0.10
MVP		0.068
MPC		0.079
ClinPred		0.036	T
GERP RS		-1.9
gMVP		0.10
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: rs371038613; hg19: chrX-51637883;