rs377062993
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate
The NM_001378120.1(MBD5):c.2828A>G(p.Gln943Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000217 in 1,613,876 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. Q943E) has been classified as Uncertain significance.
Frequency
Consequence
NM_001378120.1 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MBD5 | NM_001378120.1 | c.2828A>G | p.Gln943Arg | missense_variant | 9/14 | ENST00000642680.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MBD5 | ENST00000642680.2 | c.2828A>G | p.Gln943Arg | missense_variant | 9/14 | NM_001378120.1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152176Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000120 AC: 3AN: 249696Hom.: 0 AF XY: 0.00000741 AC XY: 1AN XY: 135040
GnomAD4 exome AF: 0.0000226 AC: 33AN: 1461700Hom.: 0 Cov.: 35 AF XY: 0.0000220 AC XY: 16AN XY: 727138
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152176Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74342
ClinVar
Submissions by phenotype
Intellectual disability, autosomal dominant 1 Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Oct 31, 2018 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 08, 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. This sequence change replaces glutamine, which is neutral and polar, with arginine, which is basic and polar, at codon 943 of the MBD5 protein (p.Gln943Arg). This variant is present in population databases (rs377062993, gnomAD 0.002%). This variant has not been reported in the literature in individuals affected with MBD5-related conditions. ClinVar contains an entry for this variant (Variation ID: 206090). 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. - |
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Feb 24, 2014 | p.Gln943Arg (CAG>CGG): c.2828 A>G in exon 10 of the MBD5 gene (NM_018328.4) The Q943R variant has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The Q943R variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is conserved in mammals; however, Arginine is observed at this position in a distantly related species. In silico analysis predicts this variant likely does not alter the protein structure/function. To our knowledge, only deletions and frameshift mutations in MBD5 have been published in association with epilepsy. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant. The variant is found in EPILEPSY panel(s). - |
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Oct 01, 2021 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at