chr11-1952162-G-T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_021134.4(MRPL23):c.176G>T(p.Gly59Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 2)

Exomes 𝑓: 0.000013 ( 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: 1.85

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.14656895).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MRPL23	NM_021134.4 link	c.176G>T	p.Gly59Val	missense_variant	Exon 3 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.176G>T	p.Gly59Val	missense_variant	Exon 3 of 5	1	NM_021134.4	ENSP00000380466.3		Q16540

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

10872

Hom.:

Cov.:

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000796

AC:

AN:

251362

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000131

AC:

AN:

152286

Hom.:

Cov.:

AF XY:

0.0000249

AC XY:

AN XY:

80180

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

2532

American (AMR)

AF:

0.00

AC:

AN:

5042

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

4570

East Asian (EAS)

AF:

0.00

AC:

AN:

6018

South Asian (SAS)

AF:

0.00

AC:

AN:

13718

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10330

Middle Eastern (MID)

AF:

0.00

AC:

AN:

656

European-Non Finnish (NFE)

AF:

0.0000198

AC:

AN:

100764

Other (OTH)

AF:

0.00

AC:

AN:

8656

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

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

AF:

0.00

AC:

AN:

10872

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

4660

African (AFR)

AF:

0.00

AC:

AN:

954

American (AMR)

AF:

0.00

AC:

AN:

572

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

364

East Asian (EAS)

AF:

0.00

AC:

AN:

186

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

456

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

8014

Other (OTH)

AF:

0.00

AC:

AN:

118

Alfa

AF:

0.0000624

Hom.:

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000119

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

May 17, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.176G>T (p.G59V) alteration is located in exon 3 (coding exon 3) of the MRPL23 gene. This alteration results from a G to T substitution at nucleotide position 176, causing the glycine (G) at amino acid position 59 to be replaced by a valine (V). 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

0.16

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.38

CADD

Benign

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.0058

T;T;T;T;T

Eigen

Benign

-0.68

Eigen_PC

Benign

-0.64

FATHMM_MKL

Uncertain

0.83

LIST_S2

Uncertain

0.86

.;D;D;D;D

M_CAP

Benign

0.010

MetaRNN

Benign

0.15

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.97

L;L;.;.;.

PhyloP100

1.9

PrimateAI

Benign

0.40

PROVEAN

Benign

-0.81

N;N;N;N;N

REVEL

Benign

0.18

Sift

Uncertain

0.0040

D;D;T;D;D

Sift4G

Uncertain

0.011

D;D;T;T;T

Polyphen

0.13

B;B;.;.;.

Vest4

0.28

MutPred

0.39

Gain of MoRF binding (P = 0.118);Gain of MoRF binding (P = 0.118);Gain of MoRF binding (P = 0.118);Gain of MoRF binding (P = 0.118);Gain of MoRF binding (P = 0.118);

MVP

0.57

MPC

0.23

ClinPred

0.18

GERP RS

2.9

Varity_R

0.11

gMVP

0.32

Mutation Taster

=87/13

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

chr11-1952162-G-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over