NM_006986.4:c.307G>A

Variant names:

• chrX-51895314-G-A
• rs141080853
• NM_006986.4:c.307G>A

Variant summary

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

The NM_006986.4(MAGED1):​c.307G>A​(p.Val103Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000531 in 1,209,678 control chromosomes in the GnomAD database, including 1 homozygotes. There are 187 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00032 (1 hom., 5 hem., cov: 23)
  • Exomes 𝑓: 0.00055 (0 hom. 182 hem.)
• Consequence: MAGED1 NM_006986.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.29
• Publications: 1 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=0.01036182).
• BP6: Variant X-51895314-G-A is Benign according to our data. Variant chrX-51895314-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2350656.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Hemizygotes in GnomAd4 at 5 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006986.4. 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.307G>A	p.Val103Met	missense	Exon 3 of 13	NP_008917.3
	MAGED1	NM_001005333.2		c.475G>A	p.Val159Met	missense	Exon 4 of 14	NP_001005333.1	Q9Y5V3-2
	MAGED1	NM_001005332.2		c.307G>A	p.Val103Met	missense	Exon 3 of 13	NP_001005332.1	Q9Y5V3-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAGED1	ENST00000326587.12	TSL:1 MANE Select	c.307G>A	p.Val103Met	missense	Exon 3 of 13	ENSP00000325333.8	Q9Y5V3-1
	MAGED1	ENST00000375695.2	TSL:1	c.475G>A	p.Val159Met	missense	Exon 4 of 14	ENSP00000364847.2	Q9Y5V3-2
	MAGED1	ENST00000898271.1		c.475G>A	p.Val159Met	missense	Exon 4 of 14	ENSP00000568330.1

Frequencies

GnomAD3 genomes AF: 0.000320 AC: 36 AN: 112391 Hom.: 1 Cov.: 23

Gnomad AFR AF: 0.000291

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: 0.000507

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000223 AC: 40 AN: 179714 AF XY: 0.000249

Gnomad AFR exome AF: 0.000233

Gnomad AMR exome AF: 0.0000368

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000636

Gnomad NFE exome AF: 0.000425

Gnomad OTH exome AF: 0.000224

GnomAD4 exome AF: 0.000552 AC: 606 AN: 1097233 Hom.: 0 Cov.: 32 AF XY: 0.000502 AC XY: 182 AN XY: 362619

African (AFR) AF: 0.0000758 AC: 2 AN: 26391

American (AMR) AF: 0.0000285 AC: 1 AN: 35137

Ashkenazi Jewish (ASJ) AF: 0.000103 AC: 2 AN: 19364

East Asian (EAS) AF: 0.00 AC: 0 AN: 30183

South Asian (SAS) AF: 0.00 AC: 0 AN: 53817

European-Finnish (FIN) AF: 0.000124 AC: 5 AN: 40471

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4136

European-Non Finnish (NFE) AF: 0.000697 AC: 587 AN: 841660

Other (OTH) AF: 0.000195 AC: 9 AN: 46074

GnomAD4 genome AF: 0.000320 AC: 36 AN: 112445 Hom.: 1 Cov.: 23 AF XY: 0.000144 AC XY: 5 AN XY: 34611

African (AFR) AF: 0.000290 AC: 9 AN: 31008

American (AMR) AF: 0.00 AC: 0 AN: 10658

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2646

East Asian (EAS) AF: 0.00 AC: 0 AN: 3566

South Asian (SAS) AF: 0.00 AC: 0 AN: 2700

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6141

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 218

European-Non Finnish (NFE) AF: 0.000507 AC: 27 AN: 53293

Other (OTH) AF: 0.00 AC: 0 AN: 1529

Alfa AF: 0.000348 Hom.: 17

Bravo AF: 0.000242

TwinsUK AF: 0.00108 AC: 4

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.000261 AC: 1

ESP6500EA AF: 0.000297 AC: 2

ExAC AF: 0.000296 AC: 36

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	0.059
BayesDel_addAF	Benign	-0.70	T
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.58
DANN	Benign	0.64
DEOGEN2	Benign	0.10	T
FATHMM_MKL	Benign	0.026	N
LIST_S2	Benign	0.59	T
M_CAP	Benign	0.0037	T
MetaRNN	Benign	0.010	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.69	N
PhyloP100		1.3
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.26	N
REVEL	Benign	0.035
Sift	Benign	1.0	T
Sift4G	Benign	0.34	T
Polyphen		0.073	B
Vest4		0.053
MVP		0.21
MPC		0.077
ClinPred		0.011	T
GERP RS		2.8
Varity_R		0.039
gMVP		0.11
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: rs141080853; hg19: chrX-51638410; COSMIC: COSV58514327; COSMIC: COSV58514327;