rs1358383505
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_001378120.1(MBD5):āc.2561A>Gā(p.Asn854Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000558 in 1,613,262 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ).
Frequency
Consequence
NM_001378120.1 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MBD5 | NM_001378120.1 | c.2561A>G | p.Asn854Ser | missense_variant | 9/14 | ENST00000642680.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MBD5 | ENST00000642680.2 | c.2561A>G | p.Asn854Ser | missense_variant | 9/14 | NM_001378120.1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000198 AC: 3AN: 151712Hom.: 0 Cov.: 32
GnomAD4 exome AF: 0.00000411 AC: 6AN: 1461550Hom.: 1 Cov.: 35 AF XY: 0.00000275 AC XY: 2AN XY: 727088
GnomAD4 genome ? AF: 0.0000198 AC: 3AN: 151712Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74052
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Feb 03, 2017 | - - |
Intellectual disability, autosomal dominant 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jun 07, 2021 | This variant is not present in population databases (ExAC no frequency). 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: "Benign"; Align-GVGD: "Class C0". The serine 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 variant has not been reported in the literature in individuals with MBD5-related conditions. ClinVar contains an entry for this variant (Variation ID: 435824). This sequence change replaces asparagine with serine at codon 854 of the MBD5 protein (p.Asn854Ser). The asparagine residue is moderately conserved and there is a small physicochemical difference between asparagine and serine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at