20-40688458-G-T
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_005461.5(MAFB):c.393C>A(p.His131Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000237 in 1,603,286 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_005461.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MAFB | NM_005461.5 | c.393C>A | p.His131Gln | missense_variant | 1/1 | ENST00000373313.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MAFB | ENST00000373313.3 | c.393C>A | p.His131Gln | missense_variant | 1/1 | NM_005461.5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000328 AC: 5AN: 152260Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000337 AC: 8AN: 237078Hom.: 0 AF XY: 0.0000309 AC XY: 4AN XY: 129528
GnomAD4 exome AF: 0.0000227 AC: 33AN: 1451026Hom.: 0 Cov.: 31 AF XY: 0.0000222 AC XY: 16AN XY: 721960
GnomAD4 genome AF: 0.0000328 AC: 5AN: 152260Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74390
ClinVar
Submissions by phenotype
Multicentric carpo-tarsal osteolysis with or without nephropathy;C4310752:Duane retraction syndrome 3 with or without deafness Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Jul 13, 2021 | - - |
MAFB-related disorder Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jul 22, 2023 | The MAFB c.393C>A variant is predicted to result in the amino acid substitution p.His131Gln. This variant has been reported in a genome-wide association study of cleft lip with and without cleft palate at higher frequencies in cases compared to controls (Beaty TH et al. 2010. PubMed ID: 20436469). This variant is reported in 0.056% of alleles in individuals of East Asian descent in gnomAD (http://gnomad.broadinstitute.org/variant/20-39317098-G-T). Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. - |
Multicentric carpo-tarsal osteolysis with or without nephropathy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 28, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Sep 27, 2022 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at