rs17435

Positions:

• chrX-154046529-T-A
• chrX-154046529-T-C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001110792.2(MECP2):​c.63-13972A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.64 (17489 hom., 19996 hem., cov: 22)
  • Failed GnomAD Quality Control
• Consequence: MECP2 NM_001110792.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.09

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]

MECP2 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MECP2	NM_001110792.2	c.63-13972A>T		intron_variant		ENST00000453960.7	NP_001104262.1
MECP2	NM_004992.4	c.27-13972A>T		intron_variant		ENST00000303391.11	NP_004983.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MECP2	ENST00000453960.7	c.63-13972A>T		intron_variant		1	NM_001110792.2	ENSP00000395535.2
MECP2	ENST00000303391.11	c.27-13972A>T		intron_variant		1	NM_004992.4	ENSP00000301948.6

Frequencies

GnomAD3 genomes AF: 0.636 AC: 69632 AN: 109564 Hom.: 17498 Cov.: 22 AF XY: 0.627 AC XY: 19974 AN XY: 31856

Gnomad AFR AF: 0.394

Gnomad AMI AF: 0.965

Gnomad AMR AF: 0.535

Gnomad ASJ AF: 0.737

Gnomad EAS AF: 0.226

Gnomad SAS AF: 0.399

Gnomad FIN AF: 0.802

Gnomad MID AF: 0.633

Gnomad NFE AF: 0.806

Gnomad OTH AF: 0.600

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

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.635 AC: 69629 AN: 109618 Hom.: 17489 Cov.: 22 AF XY: 0.626 AC XY: 19996 AN XY: 31920

Gnomad4 AFR AF: 0.393

Gnomad4 AMR AF: 0.535

Gnomad4 ASJ AF: 0.737

Gnomad4 EAS AF: 0.225

Gnomad4 SAS AF: 0.402

Gnomad4 FIN AF: 0.802

Gnomad4 NFE AF: 0.806

Gnomad4 OTH AF: 0.592

Alfa AF: 0.547 Hom.: 2350

Bravo AF: 0.602

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.33
DANN	Benign	0.81
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs17435; hg19: chrX-153311980;