16-79599008-G-C
Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PM1PM2PM5PP3_Strong
The NM_005360.5(MAF):c.895C>G(p.Arg299Gly) 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 Uncertain significance (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R299S) has been classified as Likely pathogenic.
Frequency
Consequence
NM_005360.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 10 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MAF | ENST00000326043.5 | c.895C>G | p.Arg299Gly | missense_variant | Exon 1 of 2 | 1 | NM_005360.5 | ENSP00000327048.4 | ||
MAF | ENST00000569649.1 | c.895C>G | p.Arg299Gly | missense_variant | Exon 1 of 2 | 5 | ENSP00000455097.1 | |||
MAF | ENST00000393350.1 | c.895C>G | p.Arg299Gly | missense_variant | Exon 1 of 1 | 6 | ENSP00000377019.1 |
Frequencies
GnomAD3 genomes Cov.: 30
GnomAD4 exome Cov.: 37
GnomAD4 genome Cov.: 30
ClinVar
Submissions by phenotype
MAF-related disorder Uncertain:1
The MAF c.895C>G variant is predicted to result in the amino acid substitution p.Arg299Gly. To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. Of note a different variant impacting the same amino acid (p.Arg299Ser) has been documented in patients with cataracts (Vanita et al. 2014. PubMed ID: 25064449). At this time, the clinical significance of the p.Arg229Gly variant is uncertain due to the absence of conclusive functional and genetic evidence. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.