rs1043034

Variant names:

• chrX-54810072-A-G
• rs1043034
• NM_177433.3:c.396A>G

Your query was ambiguous. Multiple possible variants found:

• chrX-54810072-A-G
• chrX-54810072-A-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_177433.3(MAGED2):​c.396A>G​(p.Thr132Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.373 in 1,203,510 control chromosomes in the GnomAD database, including 60,298 homozygotes. There are 145,279 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.45 (8802 hom., 13642 hem., cov: 21)
  • Exomes 𝑓: 0.37 (51496 hom. 131637 hem.)
• Consequence: MAGED2 NM_177433.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -4.75
• Publications: 21 publications found

Genes affected

MAGED2 (HGNC:16353): (MAGE family member D2) This gene is a member of the MAGED gene family. The MAGED genes are clustered on chromosome Xp11. This gene is located in Xp11.2, a hot spot for X-linked intellectual disability (XLID). Mutations in this gene cause a form of transient antenatal Bartter's syndrome. This gene may also be involved in several types of cancer, including breast cancer and melanoma. The protein encoded by this gene is progressively recruited from the cytoplasm to the nucleoplasm during the interphase and after nucleolar stress and is thus thought to play a role in cell cycle regulation. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2017]

MAGED2 Gene-Disease associations (from GenCC):

• Bartter disease type 5

  Inheritance: XL Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Labcorp Genetics (formerly Invitae)
• antenatal Bartter syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BP6: Variant X-54810072-A-G is Benign according to our data. Variant chrX-54810072-A-G is described in ClinVar as Benign. ClinVar VariationId is 1258035.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-4.75 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.661 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_177433.3. 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
	MAGED2	NM_177433.3	MANE Select	c.396A>G	p.Thr132Thr	synonymous	Exon 3 of 13	NP_803182.1	Q9UNF1-1
	MAGED2	NM_014599.6		c.396A>G	p.Thr132Thr	synonymous	Exon 3 of 13	NP_055414.2
	MAGED2	NM_201222.3		c.396A>G	p.Thr132Thr	synonymous	Exon 3 of 13	NP_957516.1	Q9UNF1-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAGED2	ENST00000375068.6	TSL:1 MANE Select	c.396A>G	p.Thr132Thr	synonymous	Exon 3 of 13	ENSP00000364209.1	Q9UNF1-1
	MAGED2	ENST00000375053.6	TSL:1	c.396A>G	p.Thr132Thr	synonymous	Exon 3 of 12	ENSP00000364193.2	Q9UNF1-1
	MAGED2	ENST00000375058.5	TSL:1	c.396A>G	p.Thr132Thr	synonymous	Exon 3 of 13	ENSP00000364198.1	Q9UNF1-1

Frequencies

GnomAD3 genomes AF: 0.446 AC: 48518 AN: 108902 Hom.: 8808 Cov.: 21

Gnomad AFR AF: 0.668

Gnomad AMI AF: 0.112

Gnomad AMR AF: 0.400

Gnomad ASJ AF: 0.373

Gnomad EAS AF: 0.618

Gnomad SAS AF: 0.371

Gnomad FIN AF: 0.398

Gnomad MID AF: 0.270

Gnomad NFE AF: 0.336

Gnomad OTH AF: 0.411

GnomAD2 exomes AF: 0.400 AC: 69792 AN: 174666 AF XY: 0.383

Gnomad AFR exome AF: 0.672

Gnomad AMR exome AF: 0.345

Gnomad ASJ exome AF: 0.376

Gnomad EAS exome AF: 0.629

Gnomad FIN exome AF: 0.399

Gnomad NFE exome AF: 0.344

Gnomad OTH exome AF: 0.344

GnomAD4 exome AF: 0.366 AC: 400152 AN: 1094553 Hom.: 51496 Cov.: 33 AF XY: 0.365 AC XY: 131637 AN XY: 360431

African (AFR) AF: 0.679 AC: 17902 AN: 26369

American (AMR) AF: 0.355 AC: 12348 AN: 34820

Ashkenazi Jewish (ASJ) AF: 0.379 AC: 7318 AN: 19307

East Asian (EAS) AF: 0.637 AC: 19202 AN: 30149

South Asian (SAS) AF: 0.390 AC: 20935 AN: 53718

European-Finnish (FIN) AF: 0.404 AC: 16215 AN: 40179

Middle Eastern (MID) AF: 0.322 AC: 1327 AN: 4123

European-Non Finnish (NFE) AF: 0.342 AC: 287590 AN: 839920

Other (OTH) AF: 0.377 AC: 17315 AN: 45968

GnomAD4 genome AF: 0.446 AC: 48552 AN: 108957 Hom.: 8802 Cov.: 21 AF XY: 0.436 AC XY: 13642 AN XY: 31311

African (AFR) AF: 0.669 AC: 19849 AN: 29679

American (AMR) AF: 0.399 AC: 4143 AN: 10374

Ashkenazi Jewish (ASJ) AF: 0.373 AC: 971 AN: 2602

East Asian (EAS) AF: 0.618 AC: 2103 AN: 3405

South Asian (SAS) AF: 0.367 AC: 890 AN: 2422

European-Finnish (FIN) AF: 0.398 AC: 2293 AN: 5765

Middle Eastern (MID) AF: 0.259 AC: 55 AN: 212

European-Non Finnish (NFE) AF: 0.336 AC: 17570 AN: 52339

Other (OTH) AF: 0.406 AC: 602 AN: 1482

Alfa AF: 0.375 Hom.: 22881

Bravo AF: 0.461

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	Bartter disease type 5 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.5
DANN	Benign	0.67
PhyloP100		-4.7
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: rs1043034; hg19: chrX-54836505; COSMIC: COSV54497791; COSMIC: COSV54497791;