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GeneBe

19-38932407-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_033362.4(MRPS12):c.124C>T(p.Pro42Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000000687 in 1,454,866 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 (★).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

MRPS12
NM_033362.4 missense

Scores

3
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.88
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 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.30305907).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
MRPS12NM_033362.4 linkuse as main transcriptc.124C>T p.Pro42Ser missense_variant 3/3 ENST00000308018.9
MRPS12NM_021107.1 linkuse as main transcriptc.124C>T p.Pro42Ser missense_variant 2/2
MRPS12NM_033363.1 linkuse as main transcriptc.124C>T p.Pro42Ser missense_variant 3/3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
MRPS12ENST00000308018.9 linkuse as main transcriptc.124C>T p.Pro42Ser missense_variant 3/31 NM_033362.4 P1
MRPS12ENST00000402029.3 linkuse as main transcriptc.124C>T p.Pro42Ser missense_variant 3/31 P1
MRPS12ENST00000407800.2 linkuse as main transcriptc.124C>T p.Pro42Ser missense_variant 2/21 P1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.00000410
AC:
1
AN:
243718
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
132618
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000554
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
6.87e-7
AC:
1
AN:
1454866
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
723040
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000253
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
ExAC
AF:
0.00000826
AC:
1

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 GeneticsMay 31, 2023The c.124C>T (p.P42S) alteration is located in exon 3 (coding exon 2) of the MRPS12 gene. This alteration results from a C to T substitution at nucleotide position 124, causing the proline (P) at amino acid position 42 to be replaced by a serine (S). 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
0.15
BayesDel_addAF
Benign
-0.11
T
BayesDel_noAF
Benign
-0.40
Cadd
Benign
20
Dann
Uncertain
0.99
DEOGEN2
Benign
0.12
T;T;T
Eigen
Benign
0.066
Eigen_PC
Benign
0.00047
FATHMM_MKL
Uncertain
0.90
D
M_CAP
Benign
0.023
T
MetaRNN
Benign
0.30
T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.5
L;L;L
MutationTaster
Benign
1.0
D;D;D
PrimateAI
Benign
0.41
T
PROVEAN
Uncertain
-2.6
D;D;D
REVEL
Benign
0.19
Sift
Benign
0.17
T;T;T
Sift4G
Benign
0.22
T;T;T
Polyphen
0.98
D;D;D
Vest4
0.43
MVP
0.36
MPC
1.1
ClinPred
0.83
D
GERP RS
4.9
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.085
gMVP
0.38

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs758278030; hg19: chr19-39423047; API