rs1624766

chrX-154051703-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001110792.2(MECP2):c.63-19146G>A 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 (17617 hom., 20420 hem., cov: 22)
  • Failed GnomAD Quality Control
• Consequence: MECP2 NM_001110792.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.528

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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BS2: High Homozygotes in GnomAd at 17625 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MECP2	NM_001110792.2	c.63-19146G>A		intron_variant		ENST00000453960.7
MECP2	NM_004992.4	c.27-19146G>A		intron_variant		ENST00000303391.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MECP2	ENST00000303391.11	c.27-19146G>A		intron_variant		1	NM_004992.4	P1
MECP2	ENST00000453960.7	c.63-19146G>A		intron_variant		1	NM_001110792.2

Frequencies

GnomAD3 genomes AF: 0.638 AC: 70275 AN: 110217 Hom.: 17625 Cov.: 22 AF XY: 0.628 AC XY: 20400 AN XY: 32491

Gnomad AFR AF: 0.408

Gnomad AMI AF: 0.962

Gnomad AMR AF: 0.535

Gnomad ASJ AF: 0.738

Gnomad EAS AF: 0.213

Gnomad SAS AF: 0.356

Gnomad FIN AF: 0.802

Gnomad MID AF: 0.645

Gnomad NFE AF: 0.805

Gnomad OTH AF: 0.601

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: 0.637 AC: 70272 AN: 110268 Hom.: 17617 Cov.: 22 AF XY: 0.627 AC XY: 20420 AN XY: 32552

Gnomad4 AFR AF: 0.408

Gnomad4 AMR AF: 0.535

Gnomad4 ASJ AF: 0.738

Gnomad4 EAS AF: 0.213

Gnomad4 SAS AF: 0.358

Gnomad4 FIN AF: 0.802

Gnomad4 NFE AF: 0.805

Gnomad4 OTH AF: 0.592

Alfa AF: 0.763 Hom.: 62728

Bravo AF: 0.607

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	0.94
Dann	Benign	0.64

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: rs1624766; hg19: chrX-153317154;