rs139953766
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001378120.1(MBD5):c.1962C>A(p.Asp654Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000124 in 1,613,822 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D654V) has been classified as Likely benign.
Frequency
Consequence
NM_001378120.1 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MBD5 | NM_001378120.1 | c.1962C>A | p.Asp654Glu | missense_variant | 8/14 | ENST00000642680.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MBD5 | ENST00000642680.2 | c.1962C>A | p.Asp654Glu | missense_variant | 8/14 | NM_001378120.1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152172Hom.: 0 Cov.: 32
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461650Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 727134
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152172Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74340
ClinVar
Submissions by phenotype
Intellectual disability, autosomal dominant 1 Uncertain:2
Uncertain significance, criteria provided, single submitter | curation | SIB Swiss Institute of Bioinformatics | Apr 16, 2018 | This variant is interpreted as a Uncertain Significance, for Mental retardation, autosomal dominant 1, Autosomal Dominant inheritance. The following ACMG Tag(s) were applied: PM2 => Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 04, 2021 | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0". The glutamic acid amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This sequence change replaces aspartic acid with glutamic acid at codon 654 of the MBD5 protein (p.Asp654Glu). The aspartic acid residue is highly conserved and there is a small physicochemical difference between aspartic acid and glutamic acid. This variant has been observed in individual(s) with intellectual disability (PMID: 17847001). ClinVar contains an entry for this variant (Variation ID: 549477). This variant is not present in population databases (ExAC no frequency). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at