11-59806554-C-G
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_017840.4(MRPL16):āc.549G>Cā(p.Leu183Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000039 in 1,614,128 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.0000066 ( 0 hom., cov: 32)
Exomes š: 0.000042 ( 0 hom. )
Consequence
MRPL16
NM_017840.4 missense
NM_017840.4 missense
Scores
2
11
6
Clinical Significance
Conservation
PhyloP100: 0.686
Genes affected
MRPL16 (HGNC:14476): (mitochondrial ribosomal protein L16) 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. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MRPL16 | NM_017840.4 | c.549G>C | p.Leu183Phe | missense_variant | 4/4 | ENST00000300151.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MRPL16 | ENST00000300151.5 | c.549G>C | p.Leu183Phe | missense_variant | 4/4 | 1 | NM_017840.4 | P1 | |
MRPL16 | ENST00000534340.1 | c.240G>C | p.Leu80Phe | missense_variant | 4/4 | 3 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152240Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000954 AC: 24AN: 251488Hom.: 0 AF XY: 0.000132 AC XY: 18AN XY: 135918
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GnomAD4 exome AF: 0.0000424 AC: 62AN: 1461888Hom.: 0 Cov.: 31 AF XY: 0.0000550 AC XY: 40AN XY: 727246
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GnomAD4 genome AF: 0.00000657 AC: 1AN: 152240Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74382
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 12, 2021 | The c.549G>C (p.L183F) alteration is located in exon 4 (coding exon 4) of the MRPL16 gene. This alteration results from a G to C substitution at nucleotide position 549, causing the leucine (L) at amino acid position 183 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Pathogenic
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T;T
Eigen
Uncertain
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D
M_CAP
Benign
D
MetaRNN
Uncertain
T;T
MetaSVM
Benign
T
MutationAssessor
Pathogenic
M;.
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D
REVEL
Uncertain
Sift
Uncertain
D;T
Sift4G
Benign
T;.
Polyphen
D;.
Vest4
MutPred
Loss of MoRF binding (P = 0.1239);.;
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
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