10-73250990-AC-A
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Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP5_Moderate
The NM_016065.4(MRPS16):βc.275delβ(p.Gly92ValfsTer11) variant causes a frameshift, splice region change. The variant allele was found at a frequency of 0.00000248 in 1,613,996 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Pathogenic (β ).
Frequency
Genomes: π 0.000013 ( 0 hom., cov: 32)
Exomes π: 0.0000014 ( 0 hom. )
Consequence
MRPS16
NM_016065.4 frameshift, splice_region
NM_016065.4 frameshift, splice_region
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 6.00
Genes affected
MRPS16 (HGNC:14048): (mitochondrial ribosomal protein S16) Mammalian mitochondrial ribosomal proteins are encoded by nuclear genes and help in protein synthesis within the mitochondrion. Mitochondrial ribosomes (mitoribosomes) consist of a small 28S subunit and a large 39S subunit. They have an estimated 75% protein to rRNA composition compared to prokaryotic ribosomes, where this ratio is reversed. Another difference between mammalian mitoribosomes and prokaryotic ribosomes is that the latter contain a 5S rRNA. Among different species, the proteins comprising the mitoribosome differ greatly in sequence, and sometimes in biochemical properties, which prevents easy recognition by sequence homology. This gene encodes a 28S subunit protein that belongs to the ribosomal protein S16P family. The encoded protein is one of the most highly conserved ribosomal proteins between mammalian and yeast mitochondria. Three pseudogenes (located at 8q21.3, 20q13.32, 22q12-q13.1) for this gene have been described. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 10-73250990-AC-A is Pathogenic according to our data. Variant chr10-73250990-AC-A is described in ClinVar as [Pathogenic]. Clinvar id is 214677.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MRPS16 | NM_016065.4 | c.275del | p.Gly92ValfsTer11 | frameshift_variant, splice_region_variant | 3/3 | ENST00000372945.8 | |
DNAJC9-AS1 | NR_038373.1 | n.175+2542del | intron_variant, non_coding_transcript_variant | ||||
MRPS16 | XM_047425263.1 | c.269del | p.Gly90ValfsTer11 | frameshift_variant, splice_region_variant | 3/3 | ||
MRPS16 | NM_001410935.1 | c.274+772del | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MRPS16 | ENST00000372945.8 | c.275del | p.Gly92ValfsTer11 | frameshift_variant, splice_region_variant | 3/3 | 1 | NM_016065.4 | P1 | |
DNAJC9-AS1 | ENST00000440197.2 | n.182+2542del | intron_variant, non_coding_transcript_variant | 1 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152164Hom.: 0 Cov.: 32
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GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461832Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1AN XY: 727220
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GnomAD4 genome AF: 0.0000131 AC: 2AN: 152164Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74340
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Mar 19, 2014 | c.275delG in exon 3 of the MRPS16 gene (NM_016065.3). The normal sequence with the base that is deleted in braces is:ttag{G}TCTT with the intronic bases in lower case and the exonic bases in upper case. The c.275delG mutation in the MRPS16 gene destroys the canonical splice acceptor site in exon 3. It is predicted to cause abnormal gene splicing, either leading to an abnormal message that is subject to nonsense-mediated mRNA decay, or to an abnormal protein product if the message is used for protein translation. Although this mutation has not been previously reported to our knowledge, it is expected to be pathogenic. The variant is found in MITONUC-MITOP panel(s). - |
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SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_AL_spliceai
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Find out detailed SpliceAI scores and Pangolin per-transcript scores at