rs786205221
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PM1PM2PM5PP3_StrongPP5_Moderate
The NM_005360.5(MAF):c.895C>T(p.Arg299Cys) variant causes a missense change involving the alteration of a non-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 Pathogenic (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R299G) has been classified as Uncertain significance.
Frequency
Consequence
NM_005360.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MAF | NM_005360.5 | c.895C>T | p.Arg299Cys | missense_variant | 1/2 | ENST00000326043.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MAF | ENST00000326043.5 | c.895C>T | p.Arg299Cys | missense_variant | 1/2 | 1 | NM_005360.5 | A2 | |
MAF | ENST00000569649.1 | c.895C>T | p.Arg299Cys | missense_variant | 1/2 | 5 | P4 | ||
MAF | ENST00000393350.1 | c.895C>T | p.Arg299Cys | missense_variant | 1/1 | A2 |
Frequencies
GnomAD3 genomes ? Cov.: 30
GnomAD4 exome Cov.: 37
GnomAD4 genome ? Cov.: 30
ClinVar
Submissions by phenotype
Ayme-Gripp syndrome;C1857768:Cataract 21 multiple types Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Oct 04, 2021 | For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Arg299 amino acid residue in MAF. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 17982426, 25064449). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. This missense change has been observed in individual(s) with bilateral cataracts (Invitae). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (ExAC no frequency). This sequence change replaces arginine with cysteine at codon 299 of the MAF protein (p.Arg299Cys). The arginine residue is highly conserved and there is a large physicochemical difference between arginine and cysteine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.