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.Arg111Ter) 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/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MRPS16 | NM_016065.4 | c.331C>T | p.Arg111Ter | stop_gained | 3/3 | ENST00000372945.8 | |
DNAJC9-AS1 | NR_038373.1 | n.175+2485G>A | intron_variant, non_coding_transcript_variant | ||||
MRPS16 | XM_047425263.1 | c.325C>T | p.Arg109Ter | stop_gained | 3/3 | ||
MRPS16 | NM_001410935.1 | c.274+828C>T | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MRPS16 | ENST00000372945.8 | c.331C>T | p.Arg111Ter | stop_gained | 3/3 | 1 | NM_016065.4 | P1 | |
DNAJC9-AS1 | ENST00000440197.2 | n.182+2485G>A | intron_variant, non_coding_transcript_variant | 1 |
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
Pathogenic, no assertion criteria provided | literature only | OMIM | Nov 01, 2004 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center | Sep 22, 2024 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Apr 07, 2022 | 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. 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at