Genetic Variant MAGEA3:p.Tyr145Tyr (chrX-152701267-T-C) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_005362.4(MAGEA3):c.435T>C(p.Tyr145Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00186 in 1,207,015 control chromosomes in the GnomAD database, including 18 homozygotes. There are 880 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0025 ( 4 hom., 80 hem., cov: 21)

Exomes 𝑓: 0.0018 ( 14 hom. 800 hem. )

Consequence

MAGEA3
NM_005362.4 synonymous

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.494

Publications

4 publications found

Variant links:

Genes affected

MAGEA3 (HGNC:6801): (MAGE family member A3) This gene is a member of the MAGEA gene family. The members of this family encode proteins with 50 to 80% sequence identity to each other. The promoters and first exons of the MAGEA genes show considerable variability, suggesting that the existence of this gene family enables the same function to be expressed under different transcriptional controls. The MAGEA genes are clustered at chromosomal location Xq28. They have been implicated in some hereditary disorders, such as dyskeratosis congenita. [provided by RefSeq, Jul 2008]

MAGEA3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -11 ACMG points.

BP4

Computational evidence support a benign effect (Cadd=0.416).

BP6

Variant X-152701267-T-C is Benign according to our data. Variant chrX-152701267-T-C is described in ClinVar as Benign. ClinVar VariationId is 782074.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.494 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 4 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005362.4. 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
	MAGEA3	NM_005362.4	MANE Select	c.435T>C	p.Tyr145Tyr	synonymous	Exon 3 of 3	NP_005353.1	P43357

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MAGEA3	ENST00000370278.4	TSL:1 MANE Select	c.435T>C	p.Tyr145Tyr	synonymous	Exon 3 of 3	ENSP00000359301.3	P43357
MAGEA3	ENST00000598245.2	TSL:2	c.435T>C	p.Tyr145Tyr	synonymous	Exon 3 of 3	ENSP00000473093.1	P43357
MAGEA3	ENST00000933889.1		c.435T>C	p.Tyr145Tyr	synonymous	Exon 3 of 3	ENSP00000603948.1

Frequencies

GnomAD3 genomes

AF:

0.00243

AC:

271

AN:

111547

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00365

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000471

Gnomad ASJ

AF:

0.0273

Gnomad EAS

AF:

0.00539

Gnomad SAS

AF:

0.00641

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000793

Gnomad OTH

AF:

0.00268

GnomAD4 exome

AF:

0.00180

AC:

1973

AN:

1095417

Hom.:

Cov.:

AF XY:

0.00221

AC XY:

800

AN XY:

361435

show subpopulations

African (AFR)

AF:

0.00497

AC:

131

AN:

26377

American (AMR)

AF:

0.00111

AC:

AN:

35143

Ashkenazi Jewish (ASJ)

AF:

0.0244

AC:

471

AN:

19333

East Asian (EAS)

AF:

0.00455

AC:

137

AN:

30126

South Asian (SAS)

AF:

0.00506

AC:

273

AN:

53974

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40304

Middle Eastern (MID)

AF:

0.00170

AC:

AN:

4126

European-Non Finnish (NFE)

AF:

0.000840

AC:

706

AN:

840029

Other (OTH)

AF:

0.00454

AC:

209

AN:

46005

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.401

Heterozygous variant carriers

145

193

241

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

138

184

230

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00247

AC:

276

AN:

111598

Hom.:

Cov.:

AF XY:

0.00236

AC XY:

AN XY:

33920

show subpopulations

African (AFR)

AF:

0.00380

AC:

117

AN:

30767

American (AMR)

AF:

0.000470

AC:

AN:

10636

Ashkenazi Jewish (ASJ)

AF:

0.0273

AC:

AN:

2637

East Asian (EAS)

AF:

0.00541

AC:

AN:

3515

South Asian (SAS)

AF:

0.00643

AC:

AN:

2644

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6058

Middle Eastern (MID)

AF:

0.00

AC:

AN:

214

European-Non Finnish (NFE)

AF:

0.000793

AC:

AN:

52948

Other (OTH)

AF:

0.00265

AC:

AN:

1509

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00407

Hom.:

Bravo

AF:

0.00300

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

CADD

Benign

0.42

(source)

PhyloP100

-0.49

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over