X-54810156-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_177433.3(MAGED2):c.480C>T(p.Ala160=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000202 in 1,184,272 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 57 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0011 (0 hom., 28 hem., cov: 23)
  • Exomes 𝑓: 0.00010 (0 hom. 29 hem.)
• Consequence: MAGED2 NM_177433.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.400

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

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BP6: Variant X-54810156-C-T is Benign according to our data. Variant chrX-54810156-C-T is described in ClinVar as [Benign]. Clinvar id is 2137976.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.4 with no splicing effect.
• BS2: High Hemizygotes in GnomAd at 28 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAGED2	NM_177433.3	c.480C>T	p.Ala160=	synonymous_variant	3/13	ENST00000375068.6
MAGED2	NM_014599.6	c.480C>T	p.Ala160=	synonymous_variant	3/13
MAGED2	NM_201222.3	c.480C>T	p.Ala160=	synonymous_variant	3/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAGED2	ENST00000375068.6	c.480C>T	p.Ala160=	synonymous_variant	3/13	1	NM_177433.3	P1

Frequencies

GnomAD3 genomes AF: 0.00114 AC: 127 AN: 111514 Hom.: 0 Cov.: 23 AF XY: 0.000831 AC XY: 28 AN XY: 33706

Gnomad AFR AF: 0.00399

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000282

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: 0.00

Gnomad OTH AF: 0.00133

GnomAD3 exomes AF: 0.000300 AC: 45 AN: 149773 Hom.: 0 AF XY: 0.0000706 AC XY: 3 AN XY: 42507

Gnomad AFR exome AF: 0.00396

Gnomad AMR exome AF: 0.0000854

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000104 AC: 112 AN: 1072704 Hom.: 0 Cov.: 31 AF XY: 0.0000843 AC XY: 29 AN XY: 344094

Gnomad4 AFR exome AF: 0.00359

Gnomad4 AMR exome AF: 0.0000314

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000393

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000121

Gnomad4 OTH exome AF: 0.000378

GnomAD4 genome AF: 0.00114 AC: 127 AN: 111568 Hom.: 0 Cov.: 23 AF XY: 0.000829 AC XY: 28 AN XY: 33770

Gnomad4 AFR AF: 0.00398

Gnomad4 AMR AF: 0.000282

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00131

Alfa AF: 0.000641 Hom.: 3

Bravo AF: 0.00110

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 23, 2024

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
Cadd	Benign	4.1
Dann	Benign	0.81

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: rs138895309; hg19: chrX-54836589;