11-1956275-C-T

Variant names:

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>T(p.Thr106Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000289 in 1,383,572 control chromosomes in the GnomAD database, including 1 homozygotes. 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. T106K) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000014 ( 0 hom., cov: 18)

Exomes 𝑓: 0.0000029 ( 1 hom. )

Failed GnomAD Quality Control

Consequence

MRPL23
NM_021134.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

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=0.12111163).

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.317C>T	p.Thr106Met	missense	Exon 5 of 5	NP_066957.3
MRPL23	NM_001400172.1		c.182C>T	p.Thr61Met	missense	Exon 5 of 5	NP_001387101.1
MRPL23	NM_001400174.1		c.*52C>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.317C>T	p.Thr106Met	missense	Exon 5 of 5	ENSP00000380466.3	Q16540
MRPL23	ENST00000924183.1		c.473C>T	p.Thr158Met	missense	Exon 5 of 5	ENSP00000594242.1
MRPL23	ENST00000869798.1		c.323C>T	p.Thr108Met	missense	Exon 5 of 5	ENSP00000539857.1

Frequencies

GnomAD3 genomes

AF:

0.0000143

AC:

AN:

140144

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000500

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:

0.000468

AC:

117

AN:

250230

AF XY:

0.000466

show subpopulations

Gnomad AFR exome

AF:

0.000247

Gnomad AMR exome

AF:

0.000611

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000813

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000289

AC:

AN:

1383572

Hom.:

Cov.:

AF XY:

0.00000291

AC XY:

AN XY:

687638

show subpopulations

African (AFR)

AF:

0.0000307

AC:

AN:

32590

American (AMR)

AF:

0.0000268

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:

0.0000264

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:

0.00

AC:

AN:

1065410

Other (OTH)

AF:

0.00

AC:

AN:

57020

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000143

AC:

AN:

140144

Hom.:

Cov.:

AF XY:

0.0000148

AC XY:

AN XY:

67476

show subpopulations

African (AFR)

AF:

0.0000500

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: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.000486

Hom.:

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00116

AC:

ExAC

AF:

0.000387

AC:

EpiCase

AF:

0.000764

EpiControl

AF:

0.000832

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

-0.50

BayesDel_noAF

Benign

-0.52

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0044

Eigen

Uncertain

0.23

Eigen_PC

Benign

0.21

FATHMM_MKL

Benign

0.61

LIST_S2

Uncertain

0.96

M_CAP

Benign

0.028

MetaRNN

Benign

0.12

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.3

PhyloP100

0.46

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-1.9

REVEL

Benign

0.073

Sift

Benign

0.052

Sift4G

Benign

0.083

Polyphen

1.0

Vest4

0.32

MVP

0.45

MPC

0.66

ClinPred

0.035

GERP RS

3.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.17

gMVP

0.29

Mutation Taster

=82/18

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.19

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over