chr16-368611-T-G
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_006428.5(MRPL28):āc.466A>Cā(p.Lys156Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000557 in 1,579,354 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 Uncertain significance (ā ).
Frequency
Genomes: š 0.00031 ( 0 hom., cov: 34)
Exomes š: 0.000029 ( 0 hom. )
Consequence
MRPL28
NM_006428.5 missense
NM_006428.5 missense
Scores
1
4
9
Clinical Significance
Conservation
PhyloP100: 7.61
Genes affected
MRPL28 (HGNC:14484): (mitochondrial ribosomal protein L28) 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, a part of which was originally isolated by its ability to recognize tyrosinase in an HLA-A24-restricted fashion. [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 |
---|---|---|---|---|---|---|---|
MRPL28 | NM_006428.5 | c.466A>C | p.Lys156Gln | missense_variant | 4/6 | ENST00000199706.13 | |
MRPL28 | XM_005255041.3 | c.466A>C | p.Lys156Gln | missense_variant | 4/6 | ||
MRPL28 | XM_011522351.3 | c.466A>C | p.Lys156Gln | missense_variant | 4/6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MRPL28 | ENST00000199706.13 | c.466A>C | p.Lys156Gln | missense_variant | 4/6 | 1 | NM_006428.5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000309 AC: 47AN: 152176Hom.: 0 Cov.: 34
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GnomAD3 exomes AF: 0.0000707 AC: 16AN: 226386Hom.: 0 AF XY: 0.0000575 AC XY: 7AN XY: 121776
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GnomAD4 exome AF: 0.0000287 AC: 41AN: 1427060Hom.: 0 Cov.: 34 AF XY: 0.0000269 AC XY: 19AN XY: 705360
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GnomAD4 genome AF: 0.000309 AC: 47AN: 152294Hom.: 0 Cov.: 34 AF XY: 0.000322 AC XY: 24AN XY: 74462
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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 | Sep 14, 2022 | The c.466A>C (p.K156Q) alteration is located in exon 4 (coding exon 3) of the MRPL28 gene. This alteration results from a A to C substitution at nucleotide position 466, causing the lysine (K) at amino acid position 156 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T;T;T;T;T;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
M_CAP
Benign
D
MetaRNN
Benign
T;T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
M;M;M;.;.;.
MutationTaster
Benign
D;D;D;D;D
PrimateAI
Uncertain
T
Polyphen
P;P;P;P;.;.
Vest4
0.78, 0.77
MVP
0.54
ClinPred
T
GERP RS
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Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_AG_spliceai
Position offset: -3
Find out detailed SpliceAI scores and Pangolin per-transcript scores at