Genetic Variant MRPL23:p.Thr106Arg (chr11-1956275-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_021134.4(MRPL23):c.317C>G(p.Thr106Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000723 in 1,383,572 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T106K) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000050 ( 0 hom., cov: 18)

Exomes 𝑓: 0.0000072 ( 1 hom. )

Failed GnomAD Quality Control

Consequence

MRPL23
NM_021134.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.455

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: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.12005696).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MRPL23	NM_021134.4 link	c.317C>G	p.Thr106Arg	missense_variant	Exon 5 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.317C>G	p.Thr106Arg	missense_variant	Exon 5 of 5	1	NM_021134.4	ENSP00000380466.3		Q16540

Frequencies

GnomAD3 genomes

AF:

0.0000499

AC:

AN:

140144

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000175

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:

0.00000400

AC:

AN:

250230

AF XY:

0.00000739

show subpopulations

Gnomad AFR exome

AF:

0.0000618

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000723

AC:

AN:

1383572

Hom.:

Cov.:

AF XY:

0.00000582

AC XY:

AN XY:

687638

show subpopulations

African (AFR)

AF:

0.000153

AC:

AN:

32590

American (AMR)

AF:

0.00

AC:

AN:

37296

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23926

East Asian (EAS)

AF:

0.00

AC:

AN:

37674

South Asian (SAS)

AF:

0.00

AC:

AN:

75704

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48480

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5472

European-Non Finnish (NFE)

AF:

0.00000375

AC:

AN:

1065410

Other (OTH)

AF:

0.0000175

AC:

AN:

57020

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.456

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: AS_VQSR

AF:

0.0000499

AC:

AN:

140144

Hom.:

Cov.:

AF XY:

0.0000741

AC XY:

AN XY:

67476

show subpopulations

African (AFR)

AF:

0.000175

AC:

AN:

39970

American (AMR)

AF:

0.00

AC:

AN:

12930

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3172

East Asian (EAS)

AF:

0.00

AC:

AN:

4600

South Asian (SAS)

AF:

0.00

AC:

AN:

3604

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9234

Middle Eastern (MID)

AF:

0.00

AC:

AN:

300

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

63588

Other (OTH)

AF:

0.00

AC:

AN:

1880

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.546

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000340

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.084

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.45

CADD

Benign

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.0038

T;T

Eigen

Benign

-0.089

Eigen_PC

Benign

-0.026

FATHMM_MKL

Benign

0.70

LIST_S2

Benign

0.83

.;T

M_CAP

Benign

0.018

MetaRNN

Benign

0.12

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.3

L;L

PhyloP100

0.46

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-1.3

N;N

REVEL

Benign

0.046

Sift

Benign

0.25

T;T

Sift4G

Benign

0.41

T;T

Polyphen

0.74

P;P

Vest4

0.12

MVP

0.43

MPC

0.22

ClinPred

0.12

GERP RS

3.6

Varity_R

0.51

gMVP

0.36

Mutation Taster

=85/15

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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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11-1956275-C-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over