rs5945176

Positions:

• chrX-154117689-T-G

Variant summary

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

The ENST00000631210.1(MECP2):​n.48-12651A>C variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.353 in 110,700 control chromosomes in the GnomAD database, including 5,583 homozygotes. There are 11,481 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 0.35 (5583 hom., 11481 hem., cov: 23)
• Consequence: MECP2 ENST00000631210.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.233

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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.525 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MECP2	ENST00000631210.1	n.48-12651A>C		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.353 AC: 39015 AN: 110644 Hom.: 5582 Cov.: 23 AF XY: 0.348 AC XY: 11455 AN XY: 32874

Gnomad AFR AF: 0.533

Gnomad AMI AF: 0.0540

Gnomad AMR AF: 0.243

Gnomad ASJ AF: 0.337

Gnomad EAS AF: 0.361

Gnomad SAS AF: 0.515

Gnomad FIN AF: 0.311

Gnomad MID AF: 0.356

Gnomad NFE AF: 0.272

Gnomad OTH AF: 0.330

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

GnomAD4 genome AF: 0.353 AC: 39035 AN: 110700 Hom.: 5583 Cov.: 23 AF XY: 0.349 AC XY: 11481 AN XY: 32940

Gnomad4 AFR AF: 0.532

Gnomad4 AMR AF: 0.242

Gnomad4 ASJ AF: 0.337

Gnomad4 EAS AF: 0.361

Gnomad4 SAS AF: 0.515

Gnomad4 FIN AF: 0.311

Gnomad4 NFE AF: 0.272

Gnomad4 OTH AF: 0.337

Alfa AF: 0.310 Hom.: 3067

Bravo AF: 0.355

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	2.3
DANN	Benign	0.65

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs5945176; hg19: chrX-153383163;