X-154135119-T-G

Variant names:

• chrX-154135119-T-G
• rs5987215
• ENST00000631210.1:n.47+1938A>C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000631210.1(MECP2):​n.47+1938A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.456 in 110,588 control chromosomes in the GnomAD database, including 9,784 homozygotes. There are 14,850 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.46 (9784 hom., 14850 hem., cov: 23)
• Consequence: MECP2 ENST00000631210.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.872

Genes affected

MECP2 (HGNC:6990): (methyl-CpG binding protein 2) DNA methylation is the major modification of eukaryotic genomes and plays an essential role in mammalian development. Human proteins MECP2, MBD1, MBD2, MBD3, and MBD4 comprise a family of nuclear proteins related by the presence in each of a methyl-CpG binding domain (MBD). Each of these proteins, with the exception of MBD3, is capable of binding specifically to methylated DNA. MECP2, MBD1 and MBD2 can also repress transcription from methylated gene promoters. In contrast to other MBD family members, MECP2 is X-linked and subject to X inactivation. MECP2 is dispensible in stem cells, but is essential for embryonic development. MECP2 gene mutations are the cause of most cases of Rett syndrome, a progressive neurologic developmental disorder and one of the most common causes of cognitive disability in females. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Oct 2015]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.761 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MECP2	ENST00000631210.1	n.47+1938A>C		intron_variant	Intron 1 of 2	1

Frequencies

GnomAD3 genomes AF: 0.456 AC: 50399 AN: 110534 Hom.: 9778 Cov.: 23 AF XY: 0.452 AC XY: 14796 AN XY: 32752

Gnomad AFR AF: 0.769

Gnomad AMI AF: 0.204

Gnomad AMR AF: 0.350

Gnomad ASJ AF: 0.359

Gnomad EAS AF: 0.366

Gnomad SAS AF: 0.565

Gnomad FIN AF: 0.361

Gnomad MID AF: 0.448

Gnomad NFE AF: 0.317

Gnomad OTH AF: 0.431

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.456 AC: 50457 AN: 110588 Hom.: 9784 Cov.: 23 AF XY: 0.453 AC XY: 14850 AN XY: 32816

Gnomad4 AFR AF: 0.769

Gnomad4 AMR AF: 0.350

Gnomad4 ASJ AF: 0.359

Gnomad4 EAS AF: 0.365

Gnomad4 SAS AF: 0.566

Gnomad4 FIN AF: 0.361

Gnomad4 NFE AF: 0.317

Gnomad4 OTH AF: 0.438

Alfa AF: 0.440 Hom.: 4790

Bravo AF: 0.468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.18
DANN	Benign	0.50

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs5987215; hg19: chrX-153400594;