X-54814486-C-T

Variant names:

• chrX-54814486-C-T
• rs146570264
• NM_177433.3:c.1272-175C>T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_177433.3(MAGED2):​c.1272-175C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00352 in 546,842 control chromosomes in the GnomAD database, including 31 homozygotes. There are 525 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.010 (22 hom., 319 hem., cov: 24)
  • Exomes 𝑓: 0.0017 (9 hom. 206 hem.)
• Consequence: MAGED2 NM_177433.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.586

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]

SNORA11 (HGNC:32599): (small nucleolar RNA, H/ACA box 11) Small nucleolar RNAs (snoRNAs) are small noncoding RNAs involved in RNA processing. Box H/ACA snoRNAs, such as SNORA11, direct the conversion of uridine to pseudouridine at specific residues of ribosomal RNAs or small nuclear RNAs (snRNAs) (Gu et al., 2005).[supplied by OMIM, Mar 2008]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant X-54814486-C-T is Benign according to our data. Variant chrX-54814486-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1207559.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0105 (1176/112535) while in subpopulation AFR AF= 0.036 (1115/30981). AF 95% confidence interval is 0.0342. There are 22 homozygotes in gnomad4. There are 319 alleles in male gnomad4 subpopulation. Median coverage is 24. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 22 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAGED2	NM_177433.3	c.1272-175C>T		intron_variant	Intron 10 of 12	ENST00000375068.6	NP_803182.1
MAGED2	NM_014599.6	c.1272-175C>T		intron_variant	Intron 10 of 12		NP_055414.2
MAGED2	NM_201222.3	c.1272-175C>T		intron_variant	Intron 10 of 12		NP_957516.1
SNORA11	NR_002953.1	n.117C>T		non_coding_transcript_exon_variant	Exon 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAGED2	ENST00000375068.6	c.1272-175C>T		intron_variant	Intron 10 of 12	1	NM_177433.3	ENSP00000364209.1

Frequencies

GnomAD3 genomes AF: 0.0105 AC: 1176 AN: 112486 Hom.: 22 Cov.: 24 AF XY: 0.00918 AC XY: 318 AN XY: 34644

Gnomad AFR AF: 0.0361

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00346

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000364

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000188

Gnomad OTH AF: 0.00856

GnomAD3 exomes AF: 0.00321 AC: 549 AN: 170875 Hom.: 8 AF XY: 0.00195 AC XY: 125 AN XY: 64225

Gnomad AFR exome AF: 0.0399

Gnomad AMR exome AF: 0.00245

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000210

Gnomad FIN exome AF: 0.000118

Gnomad NFE exome AF: 0.0000884

Gnomad OTH exome AF: 0.00115

GnomAD4 exome AF: 0.00172 AC: 748 AN: 434307 Hom.: 9 Cov.: 2 AF XY: 0.00131 AC XY: 206 AN XY: 157837

Gnomad4 AFR exome AF: 0.0390

Gnomad4 AMR exome AF: 0.00262

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000121

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000105

Gnomad4 OTH exome AF: 0.00364

GnomAD4 genome AF: 0.0105 AC: 1176 AN: 112535 Hom.: 22 Cov.: 24 AF XY: 0.00919 AC XY: 319 AN XY: 34703

Gnomad4 AFR AF: 0.0360

Gnomad4 AMR AF: 0.00346

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000366

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000188

Gnomad4 OTH AF: 0.00846

Alfa AF: 0.00370 Hom.: 21

Bravo AF: 0.0124

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Dec 08, 2020

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.6
DANN	Benign	0.79
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs146570264; hg19: chrX-54840919; COSMIC: COSV99514839; COSMIC: COSV99514839;