Genetic Variant MRPL23:p.Arg144Trp (chr11-1956388-C-T) – ACMG Classification: Likely_benign (-1 pts)

Variant summary

Our verdict is Likely benign. The variant received -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

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 -1 ACMG points.

BP4

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021134.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
MRPL23	NM_021134.4	MANE Select	c.430C>T	p.Arg144Trp	missense	Exon 5 of 5	NP_066957.3
MRPL23	NM_001400172.1		c.295C>T	p.Arg99Trp	missense	Exon 5 of 5	NP_001387101.1
MRPL23	NM_001400174.1		c.*165C>T		3_prime_UTR	Exon 6 of 6	NP_001387103.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MRPL23	ENST00000397298.8	TSL:1 MANE Select	c.430C>T	p.Arg144Trp	missense	Exon 5 of 5	ENSP00000380466.3	Q16540
MRPL23	ENST00000924183.1		c.586C>T	p.Arg196Trp	missense	Exon 5 of 5	ENSP00000594242.1
MRPL23	ENST00000869798.1		c.436C>T	p.Arg146Trp	missense	Exon 5 of 5	ENSP00000539857.1

Frequencies

GnomAD3 genomes

AF:

0.0000381

AC:

AN:

131376

Hom.:

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.0000253

AC:

AN:

237370

AF XY:

0.00000771

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 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

African (AFR)

AF:

0.0000350

AC:

AN:

28548

American (AMR)

AF:

0.00

AC:

AN:

24208

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20676

East Asian (EAS)

AF:

0.00

AC:

AN:

33430

South Asian (SAS)

AF:

0.00

AC:

AN:

61334

European-Finnish (FIN)

AF:

0.0000560

AC:

AN:

35742

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4812

European-Non Finnish (NFE)

AF:

0.0000501

AC:

AN:

918734

Other (OTH)

AF:

0.0000203

AC:

AN:

49260

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

African (AFR)

AF:

0.0000522

AC:

AN:

38338

American (AMR)

AF:

0.00

AC:

AN:

11908

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2954

East Asian (EAS)

AF:

0.00

AC:

AN:

4306

South Asian (SAS)

AF:

0.00

AC:

AN:

3156

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8444

Middle Eastern (MID)

AF:

0.00

AC:

AN:

266

European-Non Finnish (NFE)

AF:

0.0000505

AC:

AN:

59456

Other (OTH)

AF:

0.00

AC:

AN:

1724

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.585

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.47

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.22

Eigen

Benign

0.13

Eigen_PC

Benign

-0.049

FATHMM_MKL

Benign

0.73

LIST_S2

Uncertain

0.94

M_CAP

Benign

0.040

MetaRNN

Benign

0.33

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.4

PhyloP100

2.6

PrimateAI

Benign

0.40

PROVEAN

Pathogenic

-4.7

REVEL

Benign

0.14

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.015

Polyphen

1.0

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

Mutation Taster

=52/48

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over