11-1952785-C-G

Variant names:

• chr11-1952785-C-G
• rs780420561
• NM_021134.4:c.227C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_021134.4(MRPL23):​c.227C>G​(p.Ser76Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 0)
• Consequence: MRPL23 NM_021134.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.23
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MRPL23	NM_021134.4	c.227C>G	p.Ser76Cys	missense_variant	Exon 4 of 5	ENST00000397298.8	NP_066957.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MRPL23	ENST00000397298.8	c.227C>G	p.Ser76Cys	missense_variant	Exon 4 of 5	1	NM_021134.4	ENSP00000380466.3

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD2 exomes AF: 0.00000403 AC: 1 AN: 248188 AF XY: 0.00000744

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 0

ExAC AF: 0.00000824 AC: 1

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Apr 02, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.227C>G (p.S76C) alteration is located in exon 4 (coding exon 4) of the MRPL23 gene. This alteration results from a C to G substitution at nucleotide position 227, causing the serine (S) at amino acid position 76 to be replaced by a cysteine (C). 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	0.13
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.097	T;T;T;T;T
Eigen	Uncertain	0.34
Eigen_PC	Benign	0.21
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.64	.;T;T;T;T
M_CAP	Benign	0.044	D
MetaRNN	Uncertain	0.50	D;D;D;D;D
MetaSVM	Benign	-0.66	T
MutationAssessor	Benign	1.9	L;L;.;.;.
PhyloP100		3.2
PrimateAI	Uncertain	0.56	T
PROVEAN	Uncertain	-3.3	D;D;D;D;D
REVEL	Benign	0.18
Sift	Uncertain	0.015	D;D;D;D;D
Sift4G	Uncertain	0.016	D;D;D;D;D
Polyphen		1.0	D;D;.;.;.
Vest4		0.47
MutPred		0.51		Loss of disorder (P = 0.0132);Loss of disorder (P = 0.0132);Loss of disorder (P = 0.0132);Loss of disorder (P = 0.0132);Loss of disorder (P = 0.0132);
MVP		0.71
MPC		0.64
ClinPred		0.88	D
GERP RS		3.4
Varity_R		0.64
gMVP		0.46
Mutation Taster		=76/24	polymorphism

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

Other links and lift over

dbSNP: rs780420561; hg19: chr11-1974015;