rs777650629
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001276270.2(MBD4):āc.1667A>Gā(p.Lys556Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000186 in 1,612,706 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 (ā ā ).
Frequency
Consequence
NM_001276270.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152244Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000399 AC: 1AN: 250886Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135652
GnomAD4 exome AF: 6.85e-7 AC: 1AN: 1460462Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0AN XY: 726610
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152244Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74382
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
The p.K556R variant (also known as c.1667A>G), located in coding exon 8 of the MBD4 gene, results from an A to G substitution at nucleotide position 1667. The lysine at codon 556 is replaced by arginine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear. -
not provided Uncertain:1
This sequence change replaces lysine, which is basic and polar, with arginine, which is basic and polar, at codon 562 of the MBD4 protein (p.Lys562Arg). This variant is present in population databases (rs777650629, gnomAD 0.008%). This variant has not been reported in the literature in individuals affected with MBD4-related conditions. ClinVar contains an entry for this variant (Variation ID: 2871151). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at