rs61749706

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP6_Moderate

The NM_001110792.2(MECP2):c.583G>C(p.Gly195Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000911 in 1,098,253 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 23)

Exomes 𝑓: 0.0000091 ( 0 hom. 2 hem. )

Consequence

MECP2
NM_001110792.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: 4.46

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

BP6

Variant X-154031281-C-G is Benign according to our data. Variant chrX-154031281-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 143618.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-154031281-C-G is described in Lovd as [Benign].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MECP2	NM_001110792.2 linkuse as main transcript	c.583G>C	p.Gly195Arg	missense_variant	3/3	ENST00000453960.7
MECP2	NM_004992.4 linkuse as main transcript	c.547G>C	p.Gly183Arg	missense_variant	4/4	ENST00000303391.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MECP2	ENST00000453960.7 linkuse as main transcript	c.583G>C	p.Gly195Arg	missense_variant	3/3	1	NM_001110792.2		P51608-2
MECP2	ENST00000303391.11 linkuse as main transcript	c.547G>C	p.Gly183Arg	missense_variant	4/4	1	NM_004992.4	P1	P51608-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000546

AC:

AN:

183234

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

67726

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000122

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000911

AC:

AN:

1098253

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

363607

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000119

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Likely 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

Likely benign, criteria provided, single submitter

curation

Centre for Population Genomics, CPG

Mar 26, 2024

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 3.0, this variant is classified as likely benign. At least the following criteria are met: The variant is observed in at least 1 individual with no features of Rett Syndrome (BS2_Supporting, PMID: 16763963). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.94

BayesDel_addAF

Pathogenic

0.31

BayesDel_noAF

Pathogenic

0.21

Cadd

Uncertain

Dann

Benign

0.97

DEOGEN2

Benign

0.41

T;.;T;T

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.96

D;D;D;D

M_CAP

Pathogenic

0.77

MetaRNN

Uncertain

0.52

D;D;D;D

MetaSVM

Uncertain

0.58

MutationAssessor

Benign

1.6

L;.;.;.

MutationTaster

Benign

1.0

D;D;N

PrimateAI

Pathogenic

0.82

PROVEAN

Benign

-0.51

N;N;.;.

REVEL

Uncertain

0.56

Sift

Uncertain

0.026

D;D;.;.

Sift4G

Benign

0.15

T;D;.;D

Polyphen

0.94

P;D;.;.

Vest4

0.41

MutPred

0.31

Gain of solvent accessibility (P = 0.0037);.;Gain of solvent accessibility (P = 0.0037);.;

MVP

0.91

ClinPred

0.70

GERP RS

5.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.23

gMVP

0.41

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