Variant chrX-154021863-T-TG details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_001110792.2(MECP2):c.*8503_*8504insC variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.095 ( 397 hom., 622 hem., cov: 16)

Exomes 𝑓: 0.056 ( 0 hom. 0 hem. )

Consequence

MECP2
NM_001110792.2 3_prime_UTR

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 1.18

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP6

Variant X-154021863-T-TG is Benign according to our data. Variant chrX-154021863-T-TG is described in ClinVar as [Benign]. Clinvar id is 143289.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.187 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MECP2	NM_001110792.2 linkuse as main transcript	c.8503_8504insC		3_prime_UTR_variant	3/3	ENST00000453960.7
MECP2	NM_004992.4 linkuse as main transcript	c.8503_8504insC		3_prime_UTR_variant	4/4	ENST00000303391.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MECP2	ENST00000303391.11 linkuse as main transcript	c.8503_8504insC		3_prime_UTR_variant	4/4	1	NM_004992.4	P1	P51608-1
MECP2	ENST00000453960.7 linkuse as main transcript	c.8503_8504insC		3_prime_UTR_variant	3/3	1	NM_001110792.2		P51608-2

Frequencies

GnomAD3 genomes

AF:

0.0949

AC:

6882

AN:

72489

Hom.:

397

Cov.:

AF XY:

0.0400

AC XY:

621

AN XY:

15537

show subpopulations

Gnomad AFR

AF:

0.192

Gnomad AMI

AF:

0.0183

Gnomad AMR

AF:

0.0414

Gnomad ASJ

AF:

0.0490

Gnomad EAS

AF:

0.0248

Gnomad SAS

AF:

0.0297

Gnomad FIN

AF:

0.0437

Gnomad MID

AF:

0.0730

Gnomad NFE

AF:

0.0629

Gnomad OTH

AF:

0.0765

GnomAD4 exome

AF:

0.0556

AC:

AN:

180

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

show subpopulations

Gnomad4 FIN exome

AF:

0.0559

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0949

AC:

6884

AN:

72515

Hom.:

397

Cov.:

AF XY:

0.0400

AC XY:

622

AN XY:

15553

show subpopulations

Gnomad4 AFR

AF:

0.192

Gnomad4 AMR

AF:

0.0413

Gnomad4 ASJ

AF:

0.0490

Gnomad4 EAS

AF:

0.0249

Gnomad4 SAS

AF:

0.0296

Gnomad4 FIN

AF:

0.0437

Gnomad4 NFE

AF:

0.0629

Gnomad4 OTH

AF:

0.0755

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, no assertion criteria provided

curation

RettBASE

Mar 10, 2010

- -

Rett syndrome

Benign:1

Benign, criteria provided, single submitter

curation

Centre for Population Genomics, CPG

Oct 11, 2023

This variant has been collected from RettBASE and curated to current modified ACMG/AMP criteria. Based on the classification scheme defined by the ClinGen Rett/Angelman-like Expert Panel for Rett/AS-like Disorders Specifications to the ACMG/AMP Variant Interpretation Guidelines VCEP 2.0, this variant is classified as benign. At least the following criteria are met: The allele frequency of this variant in at least one population in gnomAD is higher than the 0.03% threshold defined by the ClinGen Rett/Angelman-like Expert Panel for Rett/AS-like Disorders VCEP 2.0 (BA1). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over