rs763275881
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_ModerateBP6BS2
The NM_001378120.1(MBD5):āc.2279A>Gā(p.His760Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000973 in 1,613,866 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H760Y) has been classified as Uncertain significance.
Frequency
Consequence
NM_001378120.1 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MBD5 | NM_001378120.1 | c.2279A>G | p.His760Arg | missense_variant | 8/14 | ENST00000642680.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MBD5 | ENST00000642680.2 | c.2279A>G | p.His760Arg | missense_variant | 8/14 | NM_001378120.1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000986 AC: 15AN: 152166Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000797 AC: 20AN: 250804Hom.: 0 AF XY: 0.0000664 AC XY: 9AN XY: 135522
GnomAD4 exome AF: 0.0000971 AC: 142AN: 1461700Hom.: 0 Cov.: 33 AF XY: 0.0000880 AC XY: 64AN XY: 727162
GnomAD4 genome ? AF: 0.0000986 AC: 15AN: 152166Hom.: 0 Cov.: 32 AF XY: 0.0000673 AC XY: 5AN XY: 74346
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 11, 2020 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Apr 21, 2015 | - - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 05, 2017 | The p.H760R variant (also known as c.2279A>G), located in coding exon 4 of the MBD5 gene, results from an A to G substitution at nucleotide position 2279. The histidine at codon 760 is replaced by arginine, an amino acid with highly similar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this variant remains unclear. - |
Intellectual disability, autosomal dominant 1 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 07, 2024 | - - |
MBD5-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jun 06, 2023 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at