Genetic Variant NM_021134.4:c.122A>G (chr11-1951003-A-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_021134.4(MRPL23):c.122A>G(p.Gln41Arg) variant causes a missense change. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 6)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

MRPL23
NM_021134.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.66

Publications

0 publications found

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]

MRPL23 links:

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ACMG classification

Classification was made for transcript

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 link	c.122A>G	p.Gln41Arg	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
MRPL23	ENST00000397298.8 link	c.122A>G	p.Gln41Arg	missense_variant	Exon 2 of 5	1	NM_021134.4	ENSP00000380466.3		Q16540

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

183432

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

94790

African (AFR)

AF:

0.00

AC:

AN:

6152

American (AMR)

AF:

0.00

AC:

AN:

4360

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

4812

East Asian (EAS)

AF:

0.00

AC:

AN:

13660

South Asian (SAS)

AF:

0.00

AC:

AN:

12158

European-Finnish (FIN)

AF:

0.00

AC:

AN:

13952

Middle Eastern (MID)

AF:

0.00

AC:

AN:

766

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

116748

Other (OTH)

AF:

0.00

AC:

AN:

10824

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Apr 04, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.122A>G (p.Q41R) alteration is located in exon 2 (coding exon 2) of the MRPL23 gene. This alteration results from a A to G substitution at nucleotide position 122, causing the glutamine (Q) at amino acid position 41 to be replaced by an arginine (R). 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

Pathogenic

0.69

BayesDel_addAF

Uncertain

0.095

BayesDel_noAF

Benign

-0.10

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.038

T;T;T;T;T

Eigen

Uncertain

0.60

Eigen_PC

Uncertain

0.55

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.91

.;D;D;D;D

M_CAP

Benign

0.034

MetaRNN

Uncertain

0.57

D;D;D;D;D

MetaSVM

Benign

-0.68

MutationAssessor

Uncertain

2.3

M;M;.;.;.

PhyloP100

5.7

PrimateAI

Uncertain

0.65

PROVEAN

Uncertain

-2.5

D;D;D;D;D

REVEL

Uncertain

0.38

Sift

Benign

0.068

T;T;T;T;T

Sift4G

Benign

0.19

T;T;D;D;D

Polyphen

1.0

D;D;.;.;.

Vest4

0.67

MutPred

0.54

Gain of methylation at Q41 (P = 0.0311);Gain of methylation at Q41 (P = 0.0311);Gain of methylation at Q41 (P = 0.0311);Gain of methylation at Q41 (P = 0.0311);Gain of methylation at Q41 (P = 0.0311);

MVP

0.61

MPC

0.72

ClinPred

0.97

GERP RS

4.5

Varity_R

0.93

gMVP

0.70

Mutation Taster

=59/41

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over