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GeneBe

19-38932476-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.

The NM_033362.4(MRPS12):c.193A>G(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 (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000096 ( 0 hom. )

Consequence

MRPS12
NM_033362.4 missense

Scores

13
5

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.20
Variant links:
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 Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
MRPS12NM_033362.4 linkuse as main transcriptc.193A>G p.Thr65Ala missense_variant 3/3 ENST00000308018.9
MRPS12NM_021107.1 linkuse as main transcriptc.193A>G p.Thr65Ala missense_variant 2/2
MRPS12NM_033363.1 linkuse as main transcriptc.193A>G p.Thr65Ala missense_variant 3/3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
MRPS12ENST00000308018.9 linkuse as main transcriptc.193A>G p.Thr65Ala missense_variant 3/31 NM_033362.4 P1
MRPS12ENST00000402029.3 linkuse as main transcriptc.193A>G p.Thr65Ala missense_variant 3/31 P1
MRPS12ENST00000407800.2 linkuse as main transcriptc.193A>G p.Thr65Ala missense_variant 2/21 P1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000958
AC:
14
AN:
1460936
Hom.:
0
Cov.:
31
AF XY:
0.0000110
AC XY:
8
AN XY:
726720
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000117
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000378

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 submitterclinical testingAmbry GeneticsApr 07, 2022The 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: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.19
BayesDel_addAF
Uncertain
0.072
D
BayesDel_noAF
Benign
-0.13
Cadd
Uncertain
24
Dann
Uncertain
1.0
DEOGEN2
Uncertain
0.58
D;D;D
Eigen
Uncertain
0.62
Eigen_PC
Uncertain
0.62
FATHMM_MKL
Uncertain
0.96
D
M_CAP
Benign
0.042
D
MetaRNN
Uncertain
0.56
D;D;D
MetaSVM
Benign
-0.74
T
MutationAssessor
Uncertain
2.6
M;M;M
MutationTaster
Benign
1.0
D;D;D
PrimateAI
Uncertain
0.53
T
PROVEAN
Uncertain
-3.9
D;D;D
REVEL
Uncertain
0.33
Sift
Uncertain
0.0060
D;D;D
Sift4G
Uncertain
0.0040
D;D;D
Polyphen
0.94
P;P;P
Vest4
0.49
MutPred
0.41
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
0.73
MPC
1.2
ClinPred
0.97
D
GERP RS
5.0
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.30
gMVP
0.43

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1703196611; hg19: chr19-39423116; API