X-54810072-A-G

Variant names:

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

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

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]

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 id is 1258035.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-54810072-A-G is described in Lovd as [Likely_benign].
• 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAGED2	NM_177433.3	c.396A>G	p.Thr132Thr	synonymous_variant	Exon 3 of 13	ENST00000375068.6	NP_803182.1
MAGED2	NM_014599.6	c.396A>G	p.Thr132Thr	synonymous_variant	Exon 3 of 13		NP_055414.2
MAGED2	NM_201222.3	c.396A>G	p.Thr132Thr	synonymous_variant	Exon 3 of 13		NP_957516.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAGED2	ENST00000375068.6	c.396A>G	p.Thr132Thr	synonymous_variant	Exon 3 of 13	1	NM_177433.3	ENSP00000364209.1

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

Gnomad4 AFR exome AF: 0.679 AC: 17902 AN: 26369

Gnomad4 AMR exome AF: 0.355 AC: 12348 AN: 34820

Gnomad4 ASJ exome AF: 0.379 AC: 7318 AN: 19307

Gnomad4 EAS exome AF: 0.637 AC: 19202 AN: 30149

Gnomad4 SAS exome AF: 0.390 AC: 20935 AN: 53718

Gnomad4 FIN exome AF: 0.404 AC: 16215 AN: 40179

Gnomad4 NFE exome AF: 0.342 AC: 287590 AN: 839920

Gnomad4 Remaining exome 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

Gnomad4 AFR AF: 0.669 AC: 0.668789 AN: 0.668789

Gnomad4 AMR AF: 0.399 AC: 0.399364 AN: 0.399364

Gnomad4 ASJ AF: 0.373 AC: 0.373174 AN: 0.373174

Gnomad4 EAS AF: 0.618 AC: 0.617621 AN: 0.617621

Gnomad4 SAS AF: 0.367 AC: 0.367465 AN: 0.367465

Gnomad4 FIN AF: 0.398 AC: 0.397745 AN: 0.397745

Gnomad4 NFE AF: 0.336 AC: 0.335696 AN: 0.335696

Gnomad4 OTH AF: 0.406 AC: 0.406208 AN: 0.406208

Alfa AF: 0.375 Hom.: 22881

Bravo AF: 0.461

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Nov 08, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Bartter disease type 5 Benign:1

Sep 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.5
DANN	Benign	0.67
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

Publications

LitVar

Other links and lift over

dbSNP: rs1043034; hg19: chrX-54836505; COSMIC: COSV54497791; COSMIC: COSV54497791;