11-1950924-C-T

Variant names:

• chr11-1950924-C-T
• rs1590046276
• NM_021134.4:c.43C>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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.27

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]

ACMG classification

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
MRPL23	NM_021134.4	c.43C>T	p.Pro15Ser	missense_variant	Exon 2 of 5	ENST00000397298.8	NP_066957.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MRPL23	ENST00000397298.8	c.43C>T	p.Pro15Ser	missense_variant	Exon 2 of 5	1	NM_021134.4	ENSP00000380466.3

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

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

Other links and lift over

dbSNP: rs1590046276; hg19: chr11-1972154;