Genetic Variant NM_021134.4:c.425C>T (chr11-1956383-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_021134.4(MRPL23):c.425C>T(p.Pro142Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00016 ( 1 hom., cov: 17)

Exomes 𝑓: 0.00013 ( 18 hom. )

Failed GnomAD Quality Control

Consequence

MRPL23
NM_021134.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.15

Publications

4 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 -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.04713735).

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.425C>T	p.Pro142Leu	missense	Exon 5 of 5	NP_066957.3
MRPL23	NM_001400172.1		c.290C>T	p.Pro97Leu	missense	Exon 5 of 5	NP_001387101.1
MRPL23	NM_001400174.1		c.*160C>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.425C>T	p.Pro142Leu	missense	Exon 5 of 5	ENSP00000380466.3	Q16540
MRPL23	ENST00000924183.1		c.581C>T	p.Pro194Leu	missense	Exon 5 of 5	ENSP00000594242.1
MRPL23	ENST00000869798.1		c.431C>T	p.Pro144Leu	missense	Exon 5 of 5	ENSP00000539857.1

Frequencies

GnomAD3 genomes

AF:

0.000157

AC:

AN:

133338

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000361

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000825

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000307

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000828

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000121

AC:

AN:

239252

AF XY:

0.000130

show subpopulations

Gnomad AFR exome

AF:

0.000323

Gnomad AMR exome

AF:

0.0000586

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000614

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000551

Gnomad OTH exome

AF:

0.000673

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000126

AC:

151

AN:

1197748

Hom.:

Cov.:

AF XY:

0.000109

AC XY:

AN XY:

595784

show subpopulations

African (AFR)

AF:

0.000691

AC:

AN:

28946

American (AMR)

AF:

0.000160

AC:

AN:

24960

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20966

East Asian (EAS)

AF:

0.00

AC:

AN:

33808

South Asian (SAS)

AF:

0.0000479

AC:

AN:

62616

European-Finnish (FIN)

AF:

0.00

AC:

AN:

36852

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4892

European-Non Finnish (NFE)

AF:

0.000126

AC:

118

AN:

934668

Other (OTH)

AF:

0.000120

AC:

AN:

50040

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

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:

0.000157

AC:

AN:

133338

Hom.:

Cov.:

AF XY:

0.000157

AC XY:

AN XY:

63822

show subpopulations

African (AFR)

AF:

0.000361

AC:

AN:

38742

American (AMR)

AF:

0.0000825

AC:

AN:

12122

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2990

East Asian (EAS)

AF:

0.00

AC:

AN:

4356

South Asian (SAS)

AF:

0.000307

AC:

AN:

3256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8646

Middle Eastern (MID)

AF:

0.00

AC:

AN:

274

European-Non Finnish (NFE)

AF:

0.0000828

AC:

AN:

60354

Other (OTH)

AF:

0.00

AC:

AN:

1762

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

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:

0.000226

Hom.:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000116

AC:

EpiCase

AF:

0.0000546

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

0.11

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.50

CADD

Benign

(source)

DANN

Benign

0.83

DEOGEN2

Benign

0.022

Eigen

Benign

-0.61

Eigen_PC

Benign

-0.60

FATHMM_MKL

Benign

0.74

LIST_S2

Benign

0.86

M_CAP

Benign

0.021

MetaRNN

Benign

0.047

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.0

PhyloP100

2.1

PrimateAI

Benign

0.43

PROVEAN

Uncertain

-3.9

REVEL

Benign

0.11

Sift

Benign

0.17

Sift4G

Benign

0.16

Polyphen

0.046

Vest4

0.17

MVP

0.47

MPC

0.17

ClinPred

0.033

GERP RS

2.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.072

gMVP

0.37

Mutation Taster

=61/39

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