17-81703574-A-G
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_002949.4(MRPL12):āc.73A>Gā(p.Arg25Gly) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000125 in 1,440,566 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Consequence
NM_002949.4 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MRPL12 | NM_002949.4 | c.73A>G | p.Arg25Gly | missense_variant, splice_region_variant | 1/5 | ENST00000333676.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MRPL12 | ENST00000333676.8 | c.73A>G | p.Arg25Gly | missense_variant, splice_region_variant | 1/5 | 1 | NM_002949.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000657 AC: 10AN: 152152Hom.: 0 Cov.: 33
GnomAD4 exome AF: 0.00000621 AC: 8AN: 1288414Hom.: 0 Cov.: 31 AF XY: 0.00000633 AC XY: 4AN XY: 631832
GnomAD4 genome AF: 0.0000657 AC: 10AN: 152152Hom.: 0 Cov.: 33 AF XY: 0.0000673 AC XY: 5AN XY: 74346
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jul 22, 2022 | This variant is present in population databases (rs767111957, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with MRPL12-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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. This sequence change replaces arginine, which is basic and polar, with glycine, which is neutral and non-polar, at codon 25 of the MRPL12 protein (p.Arg25Gly). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at