chr20-40688642-G-A
Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PM1PM2PM5PP3_ModeratePP5_Moderate
The NM_005461.5(MAFB):c.209C>T(p.Ser70Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S70A) has been classified as Likely pathogenic.
Frequency
Consequence
NM_005461.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 10 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD4 exome Cov.: 31
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Inborn genetic diseases Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 06, 2019 | - - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Aug 12, 2024 | This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 70 of the MAFB protein (p.Ser70Leu). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with multicentric carpotarsal osteolysis syndrome (PMID: 22387013). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 30770). 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 expected to disrupt MAFB protein function with a positive predictive value of 80%. For these reasons, this variant has been classified as Pathogenic. - |
Multicentric carpo-tarsal osteolysis with or without nephropathy Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Mar 09, 2012 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at