rs201337850
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_020191.4(MRPS22):c.489T>G(p.Tyr163Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000248 in 1,614,038 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 Pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000014 ( 0 hom. )
Consequence
MRPS22
NM_020191.4 stop_gained
NM_020191.4 stop_gained
Scores
1
2
4
Clinical Significance
Conservation
PhyloP100: -0.586
Genes affected
MRPS22 (HGNC:14508): (mitochondrial ribosomal protein S22) 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 does not seem to have a counterpart in prokaryotic and fungal-mitochondrial ribosomes. This gene lies telomeric of and is transcribed in the opposite direction from the forkhead box L2 gene. A pseudogene corresponding to this gene is found on chromosome Xq. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 12 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 3-139348309-T-G is Pathogenic according to our data. Variant chr3-139348309-T-G is described in ClinVar as [Pathogenic]. Clinvar id is 521613.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MRPS22 | NM_020191.4 | c.489T>G | p.Tyr163Ter | stop_gained | 3/8 | ENST00000680020.1 | |
MRPS22 | NM_001363893.1 | c.486T>G | p.Tyr162Ter | stop_gained | 3/8 | ||
MRPS22 | NM_001363857.1 | c.366T>G | p.Tyr122Ter | stop_gained | 3/8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MRPS22 | ENST00000680020.1 | c.489T>G | p.Tyr163Ter | stop_gained | 3/8 | NM_020191.4 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152240Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.00000398 AC: 1AN: 250974Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135652
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GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461680Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 727146
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GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152358Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74508
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Inborn genetic diseases Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 27, 2017 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
Cadd
Pathogenic
Dann
Uncertain
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
MutationTaster
Benign
A;A;A;A
Vest4
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Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at