rs781805017

Variant names:

• chrX-51894655-A-G
• rs781805017
• ENST00000375695.2:c.74A>G

Your query was ambiguous. Multiple possible variants found:

• chrX-51894655-A-G
• chrX-51894655-A-C

Variant summary

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

The NM_001005333.2(MAGED1):​c.74A>G​(p.His25Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000465 in 1,074,162 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 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 0.0 (0 hom., 0 hem., cov: 20)
  • Exomes 𝑓: 0.0000047 (0 hom. 3 hem.)
  • Failed GnomAD Quality Control
• Consequence: MAGED1 NM_001005333.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.266
• 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=0.018374711).
• BP6: Variant X-51894655-A-G is Benign according to our data. Variant chrX-51894655-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2264619.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Hemizygotes in GnomAdExome4 at 3 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.45+306A>G		intron	N/A	NP_008917.3
	MAGED1	NM_001005333.2		c.74A>G	p.His25Arg	missense	Exon 3 of 14	NP_001005333.1	Q9Y5V3-2
	MAGED1	NM_001005332.2		c.45+306A>G		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.74A>G	p.His25Arg	missense	Exon 3 of 14	ENSP00000364847.2	Q9Y5V3-2
	MAGED1	ENST00000326587.12	TSL:1 MANE Select	c.45+306A>G		intron	N/A	ENSP00000325333.8	Q9Y5V3-1
	MAGED1	ENST00000898271.1		c.74A>G	p.His25Arg	missense	Exon 3 of 14	ENSP00000568330.1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 96542 Hom.: 0 Cov.: 20

Gnomad AFR AF: 0.00

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: 0.00000636 AC: 1 AN: 157143 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: 0.0000883

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000465 AC: 5 AN: 1074162 Hom.: 0 Cov.: 33 AF XY: 0.00000865 AC XY: 3 AN XY: 346820

African (AFR) AF: 0.00 AC: 0 AN: 24926

American (AMR) AF: 0.00 AC: 0 AN: 30553

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18928

East Asian (EAS) AF: 0.0000341 AC: 1 AN: 29345

South Asian (SAS) AF: 0.00 AC: 0 AN: 50643

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40021

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3956

European-Non Finnish (NFE) AF: 0.00000120 AC: 1 AN: 830714

Other (OTH) AF: 0.0000666 AC: 3 AN: 45076

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 96542 Hom.: 0 Cov.: 20 AF XY: 0.00 AC XY: 0 AN XY: 24244

African (AFR) AF: 0.00 AC: 0 AN: 25626

American (AMR) AF: 0.00 AC: 0 AN: 9001

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2426

East Asian (EAS) AF: 0.00 AC: 0 AN: 3009

South Asian (SAS) AF: 0.00 AC: 0 AN: 1927

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4466

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 187

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 47991

Other (OTH) AF: 0.00 AC: 0 AN: 1294

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.00000824 AC: 1

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	0.11
BayesDel_addAF	Benign	-0.63	T
BayesDel_noAF	Benign	-1.1
CADD	Benign	6.9
DANN	Benign	0.13
FATHMM_MKL	Benign	0.0077	N
LIST_S2	Benign	0.28	T
M_CAP	Benign	0.0067	T
MetaRNN	Benign	0.018	T
MetaSVM	Benign	-0.93	T
PhyloP100		-0.27
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-0.14	N
REVEL	Benign	0.11
Sift	Benign	0.95	T
Sift4G	Benign	0.32	T
Polyphen		0.0	B
Vest4		0.080
MutPred		0.099		Loss of catalytic residue at H25 (P = 0.0792)
MVP		0.068
MPC		0.094
ClinPred		0.0057	T
GERP RS		-3.9
gMVP		0.085
Mutation Taster		=95/5	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs781805017; hg19: chrX-51637751;