rs907317201
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_001378120.1(MBD5):c.2621C>A(p.Ala874Glu) variant causes a missense change. The variant allele was found at a frequency of 0.0000031 in 1,613,836 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. A874S) 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 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MBD5 | NM_001378120.1 | c.2621C>A | p.Ala874Glu | missense_variant | 9/14 | ENST00000642680.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MBD5 | ENST00000642680.2 | c.2621C>A | p.Ala874Glu | missense_variant | 9/14 | NM_001378120.1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 151980Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251282Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135806
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461856Hom.: 0 Cov.: 35 AF XY: 0.00 AC XY: 0AN XY: 727228
GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 151980Hom.: 0 Cov.: 32 AF XY: 0.0000539 AC XY: 4AN XY: 74220
ClinVar
Submissions by phenotype
Intellectual disability, autosomal dominant 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Feb 27, 2023 | Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt MBD5 protein function. 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. ClinVar contains an entry for this variant (Variation ID: 581611). This variant has not been reported in the literature in individuals affected with MBD5-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.007%). This sequence change replaces alanine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 874 of the MBD5 protein (p.Ala874Glu). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at