rs62707562

chrX-154030626-C-GchrX-154030626-C-T

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2 BP4 BP6_Moderate

The NM_001110792.2(MECP2):c.1238G>C(p.Ser413Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S413N) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 20)
• Consequence: MECP2 NM_001110792.2 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.53

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 Likely_benign. Variant got -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.28278506).
• BP6: Variant X-154030626-C-G is Benign according to our data. Variant chrX-154030626-C-G is described in ClinVar as [Benign]. Clinvar id is 158881.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MECP2	NM_001110792.2	c.1238G>C	p.Ser413Thr	missense_variant	3/3	ENST00000453960.7
MECP2	NM_004992.4	c.1202G>C	p.Ser401Thr	missense_variant	4/4	ENST00000303391.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MECP2	ENST00000453960.7	c.1238G>C	p.Ser413Thr	missense_variant	3/3	1	NM_001110792.2
MECP2	ENST00000303391.11	c.1202G>C	p.Ser401Thr	missense_variant	4/4	1	NM_004992.4	P1
MECP2	ENST00000407218.5	c.*574G>C		3_prime_UTR_variant	4/4	5
MECP2	ENST00000628176.2	c.*574G>C		3_prime_UTR_variant	5/5	3

Frequencies

GnomAD3 genomes Cov.: 20

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 20

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Feb 08, 2013

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.093
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Benign	-0.090
Cadd	Benign	20
Dann	Benign	0.97
DEOGEN2	Benign	0.088	T
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.25	T
M_CAP	Pathogenic	0.54	D
MetaRNN	Benign	0.28	T
MetaSVM	Uncertain	-0.048	T
MutationTaster	Benign	0.57	D;N
ClinPred		0.31	T
GERP RS		5.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs62707562; hg19: chrX-153296077;