chr19-38932476-A-G
Position:
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_033362.4(MRPS12):āc.193A>Gā(p.Thr65Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00000958 in 1,460,936 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: not found (cov: 32)
Exomes š: 0.0000096 ( 0 hom. )
Consequence
MRPS12
NM_033362.4 missense
NM_033362.4 missense
Scores
13
5
Clinical Significance
Conservation
PhyloP100: 7.20
Genes affected
MRPS12 (HGNC:10380): (mitochondrial ribosomal protein S12) 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 S12P family. The encoded protein is a key component of the ribosomal small subunit and controls the decoding fidelity and susceptibility to aminoglycoside antibiotics. The gene for mitochondrial seryl-tRNA synthetase is located upstream and adjacent to this gene, and both genes are possible candidates for the autosomal dominant deafness gene (DFNA4). Splice variants that differ in the 5' UTR have been found for this gene; all three variants encode the same protein. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -4 ACMG points.
BS2
?
High AC in GnomAdExome4 at 14 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MRPS12 | NM_033362.4 | c.193A>G | p.Thr65Ala | missense_variant | 3/3 | ENST00000308018.9 | |
MRPS12 | NM_021107.1 | c.193A>G | p.Thr65Ala | missense_variant | 2/2 | ||
MRPS12 | NM_033363.1 | c.193A>G | p.Thr65Ala | missense_variant | 3/3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MRPS12 | ENST00000308018.9 | c.193A>G | p.Thr65Ala | missense_variant | 3/3 | 1 | NM_033362.4 | P1 | |
MRPS12 | ENST00000402029.3 | c.193A>G | p.Thr65Ala | missense_variant | 3/3 | 1 | P1 | ||
MRPS12 | ENST00000407800.2 | c.193A>G | p.Thr65Ala | missense_variant | 2/2 | 1 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome AF: 0.00000958 AC: 14AN: 1460936Hom.: 0 Cov.: 31 AF XY: 0.0000110 AC XY: 8AN XY: 726720
GnomAD4 exome
AF:
AC:
14
AN:
1460936
Hom.:
Cov.:
31
AF XY:
AC XY:
8
AN XY:
726720
Gnomad4 AFR exome
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GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
Bravo
AF:
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 | Apr 07, 2022 | The c.193A>G (p.T65A) alteration is located in exon 3 (coding exon 2) of the MRPS12 gene. This alteration results from a A to G substitution at nucleotide position 193, causing the threonine (T) at amino acid position 65 to be replaced by an alanine (A). 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
Uncertain
D
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Uncertain
D;D;D
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
M_CAP
Benign
D
MetaRNN
Uncertain
D;D;D
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M;M
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D;D
REVEL
Uncertain
Sift
Uncertain
D;D;D
Sift4G
Uncertain
D;D;D
Polyphen
P;P;P
Vest4
MutPred
Loss of phosphorylation at T65 (P = 0.0334);Loss of phosphorylation at T65 (P = 0.0334);Loss of phosphorylation at T65 (P = 0.0334);
MVP
MPC
1.2
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at