10-73250935-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_016065.4(MRPS16):c.331C>T(p.Arg111*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000062 in 1,613,966 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. R111R) has been classified as Likely pathogenic.
Frequency
Consequence
NM_016065.4 stop_gained
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 rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MRPS16 | NM_016065.4 | c.331C>T | p.Arg111* | stop_gained | Exon 3 of 3 | ENST00000372945.8 | NP_057149.1 | |
MRPS16 | XM_047425263.1 | c.325C>T | p.Arg109* | stop_gained | Exon 3 of 3 | XP_047281219.1 | ||
MRPS16 | NM_001410935.1 | c.274+828C>T | intron_variant | Intron 2 of 2 | NP_001397864.1 | |||
DNAJC9-AS1 | NR_038373.1 | n.175+2485G>A | intron_variant | Intron 2 of 3 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152120Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000159 AC: 4AN: 251474Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135914
GnomAD4 exome AF: 0.00000616 AC: 9AN: 1461846Hom.: 0 Cov.: 30 AF XY: 0.00000413 AC XY: 3AN XY: 727234
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152120Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74296
ClinVar
Submissions by phenotype
Combined oxidative phosphorylation defect type 2 Pathogenic:1Uncertain:1
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not provided Uncertain:1
This sequence change creates a premature translational stop signal (p.Arg111*) in the MRPS16 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 27 amino acid(s) of the MRPS16 protein. This variant is present in population databases (rs104894168, gnomAD 0.01%). This premature translational stop signal has been observed in individual(s) with clinical features of combined oxidative phosphorylation deficiency (PMID: 15505824, 28749478). ClinVar contains an entry for this variant (Variation ID: 1835). Studies have shown that this premature translational stop signal alters MRPS16 gene expression (PMID: 18539099). 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. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at