Variant 11-1956388-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP4

The NM_021134.4(MRPL23):c.430C>T(p.Arg144Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R144Q) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000038 ( 0 hom., cov: 17)

Exomes 𝑓: 0.000042 ( 3 hom. )

Failed GnomAD Quality Control

Consequence

MRPL23
NM_021134.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.63

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 made for transcript

Verdict is Likely_benign. Variant got -1 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.32963994).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MRPL23	NM_021134.4 linkuse as main transcript	c.430C>T	p.Arg144Trp	missense_variant	5/5	ENST00000397298.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MRPL23	ENST00000397298.8 linkuse as main transcript	c.430C>T	p.Arg144Trp	missense_variant	5/5	1	NM_021134.4	P1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

131376

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.0000522

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:

0.0000505

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000253

AC:

AN:

237370

Hom.:

AF XY:

0.00000771

AC XY:

AN XY:

129704

show subpopulations

Gnomad AFR exome

AF:

0.0000652

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000629

Gnomad NFE exome

AF:

0.0000277

Gnomad OTH exome

AF:

0.000169

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000425

AC:

AN:

1176744

Hom.:

Cov.:

AF XY:

0.0000427

AC XY:

AN XY:

585484

show subpopulations

Gnomad4 AFR exome

AF:

0.0000350

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000560

Gnomad4 NFE exome

AF:

0.0000501

Gnomad4 OTH exome

AF:

0.0000203

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000381

AC:

AN:

131376

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

62818

show subpopulations

Gnomad4 AFR

AF:

0.0000522

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000505

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000248

AC:

EpiCase

AF:

0.00

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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 05, 2022

The c.430C>T (p.R144W) alteration is located in exon 5 (coding exon 5) of the MRPL23 gene. This alteration results from a C to T substitution at nucleotide position 430, causing the arginine (R) at amino acid position 144 to be replaced by a tryptophan (W). 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

0.12

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.47

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.22

T;T

Eigen

Benign

0.13

Eigen_PC

Benign

-0.049

FATHMM_MKL

Benign

0.73

LIST_S2

Uncertain

0.94

.;D

M_CAP

Benign

0.040

MetaRNN

Benign

0.33

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.4

M;M

MutationTaster

Benign

1.0

D;D;D;D;D

PrimateAI

Benign

0.40

PROVEAN

Pathogenic

-4.7

D;D

REVEL

Benign

0.14

Sift

Uncertain

0.0020

D;D

Sift4G

Uncertain

0.015

D;D

Polyphen

1.0

D;D

Vest4

0.20

MVP

0.52

MPC

0.68

ClinPred

0.98

GERP RS

2.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.20

gMVP

0.58

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over