11-1950924-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 1P and 0B. PP3

The NM_021134.4(MRPL23):​c.43C>T​(p.Pro15Ser) variant causes a missense change. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 5)

Consequence

MRPL23
NM_021134.4 missense

Scores

5
10
4

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.27
Variant links:
Genes affected
MRPL23 (HGNC:10322): (mitochondrial ribosomal protein L23) 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. The gene is biallelically expressed, despite its location within a region of imprinted genes on chromosome 11. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PP3
MetaRNN computational evidence supports a deleterious effect, 0.826

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MRPL23NM_021134.4 linkc.43C>T p.Pro15Ser missense_variant Exon 2 of 5 ENST00000397298.8 NP_066957.3 Q16540A0A024RCB2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MRPL23ENST00000397298.8 linkc.43C>T p.Pro15Ser missense_variant Exon 2 of 5 1 NM_021134.4 ENSP00000380466.3 Q16540

Frequencies

GnomAD3 genomes
Cov.:
5
GnomAD4 exome
Cov.:
0
GnomAD4 genome
Cov.:
5

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Feb 22, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.43C>T (p.P15S) alteration is located in exon 2 (coding exon 2) of the MRPL23 gene. This alteration results from a C to T substitution at nucleotide position 43, causing the proline (P) at amino acid position 15 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
Uncertain
0.54
BayesDel_addAF
Uncertain
0.089
D
BayesDel_noAF
Benign
-0.11
CADD
Pathogenic
26
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.15
T;T;T;T;T
Eigen
Pathogenic
0.75
Eigen_PC
Uncertain
0.65
FATHMM_MKL
Uncertain
0.89
D
LIST_S2
Uncertain
0.94
.;D;D;D;D
M_CAP
Uncertain
0.098
D
MetaRNN
Pathogenic
0.83
D;D;D;D;D
MetaSVM
Benign
-0.60
T
MutationAssessor
Uncertain
2.8
M;M;.;.;.
PrimateAI
Uncertain
0.73
T
PROVEAN
Pathogenic
-7.3
D;D;D;D;D
REVEL
Uncertain
0.63
Sift
Pathogenic
0.0
D;D;D;D;D
Sift4G
Uncertain
0.0060
D;D;D;D;D
Polyphen
1.0
D;D;.;.;.
Vest4
0.72
MutPred
0.73
Gain of MoRF binding (P = 0.0425);Gain of MoRF binding (P = 0.0425);Gain of MoRF binding (P = 0.0425);Gain of MoRF binding (P = 0.0425);Gain of MoRF binding (P = 0.0425);
MVP
0.68
MPC
0.70
ClinPred
1.0
D
GERP RS
4.5
Varity_R
0.93
gMVP
0.47

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: rs1590046276; hg19: chr11-1972154; API