NM_020932.3:c.374G>A

Variant names:

• chrX-76428304-G-A
• rs146995693
• NM_020932.3:c.374G>A

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_020932.3(MAGEE1):​c.374G>A​(p.Cys125Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00878 in 1,209,800 control chromosomes in the GnomAD database, including 50 homozygotes. There are 3,418 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0068 (9 hom., 216 hem., cov: 26)
  • Exomes 𝑓: 0.0090 (41 hom. 3202 hem.)
• Consequence: MAGEE1 NM_020932.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.421
• Publications: 5 publications found

Genes affected

MAGEE1 (HGNC:24934): (MAGE family member E1) This gene encodes an alpha-dystrobrevin-associated MAGE (melanoma-associated antigen) protein, which is a member of the MAGE family. The protein contains a nuclear localization signal in the N-terminus, 30 12-amino acid repeats beginning at nt 60 with the consensus sequence ASEGPSTSVLPT, and two MAGE domains in the C-terminus. It may play a signaling role in brain, muscle, and peripheral nerve. This gene is located on X chromosome in a region containing loci linked to cognitive disability. [provided by RefSeq, Mar 2010]

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.002328813).
• BP6: Variant X-76428304-G-A is Benign according to our data. Variant chrX-76428304-G-A is described in ClinVar as Benign. ClinVar VariationId is 790293.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 9 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020932.3. 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
	MAGEE1	NM_020932.3	MANE Select	c.374G>A	p.Cys125Tyr	missense	Exon 1 of 1	NP_065983.1	Q9HCI5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAGEE1	ENST00000361470.4	TSL:6 MANE Select	c.374G>A	p.Cys125Tyr	missense	Exon 1 of 1	ENSP00000354912.2	Q9HCI5

Frequencies

GnomAD3 genomes AF: 0.00682 AC: 763 AN: 111879 Hom.: 9 Cov.: 26

Gnomad AFR AF: 0.00117

Gnomad AMI AF: 0.119

Gnomad AMR AF: 0.000929

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0178

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00996

Gnomad OTH AF: 0.000663

GnomAD2 exomes AF: 0.00671 AC: 1215 AN: 180939 AF XY: 0.00663

Gnomad AFR exome AF: 0.00163

Gnomad AMR exome AF: 0.000585

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0239

Gnomad NFE exome AF: 0.00954

Gnomad OTH exome AF: 0.00492

GnomAD4 exome AF: 0.00898 AC: 9858 AN: 1097870 Hom.: 41 Cov.: 33 AF XY: 0.00881 AC XY: 3202 AN XY: 363392

African (AFR) AF: 0.00117 AC: 31 AN: 26400

American (AMR) AF: 0.000568 AC: 20 AN: 35192

Ashkenazi Jewish (ASJ) AF: 0.000310 AC: 6 AN: 19372

East Asian (EAS) AF: 0.00 AC: 0 AN: 30198

South Asian (SAS) AF: 0.000462 AC: 25 AN: 54134

European-Finnish (FIN) AF: 0.0222 AC: 894 AN: 40263

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

European-Non Finnish (NFE) AF: 0.0102 AC: 8616 AN: 842084

Other (OTH) AF: 0.00577 AC: 266 AN: 46091

GnomAD4 genome AF: 0.00682 AC: 763 AN: 111930 Hom.: 9 Cov.: 26 AF XY: 0.00630 AC XY: 216 AN XY: 34296

African (AFR) AF: 0.00117 AC: 36 AN: 30846

American (AMR) AF: 0.000928 AC: 10 AN: 10779

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2642

East Asian (EAS) AF: 0.00 AC: 0 AN: 3516

South Asian (SAS) AF: 0.00 AC: 0 AN: 2686

European-Finnish (FIN) AF: 0.0178 AC: 110 AN: 6182

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 211

European-Non Finnish (NFE) AF: 0.00997 AC: 527 AN: 52881

Other (OTH) AF: 0.000656 AC: 1 AN: 1525

Alfa AF: 0.00829 Hom.: 347

Bravo AF: 0.00551

TwinsUK AF: 0.00971 AC: 36

ALSPAC AF: 0.0125 AC: 36

ESP6500AA AF: 0.00183 AC: 7

ESP6500EA AF: 0.00907 AC: 61

ExAC AF: 0.00647 AC: 786

EpiCase AF: 0.00802

EpiControl AF: 0.00872

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.096
BayesDel_addAF	Benign	-0.85	T
BayesDel_noAF	Benign	-0.98
CADD	Benign	12
DANN	Benign	0.40
DEOGEN2	Benign	0.0073	T
FATHMM_MKL	Benign	0.010	N
LIST_S2	Benign	0.39	T
MetaRNN	Benign	0.0023	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.69	N
PhyloP100		-0.42
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.22	N
REVEL	Benign	0.0090
Sift	Benign	0.089	T
Sift4G	Benign	0.13	T
Polyphen		0.28	B
Vest4		0.031
MVP		0.043
MPC		0.67
ClinPred		0.0016	T
GERP RS		-3.9
Varity_R		0.094
gMVP		0.30
Mutation Taster		=100/0	polymorphism (auto)

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: rs146995693; hg19: chrX-75648697;