17-81703456-C-T
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Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate
The NM_002949.4(MRPL12):c.-46C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000357 in 1,464,478 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.00022 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00037 ( 0 hom. )
Consequence
MRPL12
NM_002949.4 5_prime_UTR
NM_002949.4 5_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.71
Genes affected
MRPL12 (HGNC:10378): (mitochondrial ribosomal protein L12) 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 39S subunit protein which forms homodimers. In prokaryotic ribosomes, two L7/L12 dimers and one L10 protein form the L8 protein complex. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.26).
BP6
Variant 17-81703456-C-T is Benign according to our data. Variant chr17-81703456-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 385422.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MRPL12 | NM_002949.4 | c.-46C>T | 5_prime_UTR_variant | 1/5 | ENST00000333676.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MRPL12 | ENST00000333676.8 | c.-46C>T | 5_prime_UTR_variant | 1/5 | 1 | NM_002949.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000223 AC: 34AN: 152248Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000179 AC: 14AN: 78094Hom.: 0 AF XY: 0.000222 AC XY: 10AN XY: 44966
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GnomAD4 exome AF: 0.000373 AC: 489AN: 1312230Hom.: 0 Cov.: 27 AF XY: 0.000363 AC XY: 235AN XY: 647122
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GnomAD4 genome AF: 0.000223 AC: 34AN: 152248Hom.: 0 Cov.: 33 AF XY: 0.000188 AC XY: 14AN XY: 74378
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jan 22, 2018 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Computational scores
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Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at