Genetic Variant MRPL23:p.Pro90Leu (chr11-1952827-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.269C>T(p.Pro90Leu) 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 (★).

Frequency

Genomes: not found (cov: 0)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

MRPL23
NM_021134.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.44

Publications

1 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=0.33801603).

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	UniProt
MRPL23	NM_021134.4	MANE Select	c.269C>T	p.Pro90Leu	missense	Exon 4 of 5	NP_066957.3
MRPL23	NM_001400176.1		c.269C>T	p.Pro90Leu	missense	Exon 4 of 7	NP_001387105.1
MRPL23	NM_001400179.1		c.269C>T	p.Pro90Leu	missense	Exon 4 of 6	NP_001387108.1	A8MYK1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MRPL23	ENST00000397298.8	TSL:1 MANE Select	c.269C>T	p.Pro90Leu	missense	Exon 4 of 5	ENSP00000380466.3	Q16540
MRPL23	ENST00000924183.1		c.269C>T	p.Pro90Leu	missense	Exon 4 of 5	ENSP00000594242.1
MRPL23	ENST00000397297.7	TSL:2	c.269C>T	p.Pro90Leu	missense	Exon 4 of 6	ENSP00000380465.3	A8MYK1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000240

AC:

AN:

250084

AF XY:

0.0000295

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000545

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000266

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

714

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

384

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

552

Other (OTH)

AF:

0.00

AC:

AN:

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000611

Hom.:

ExAC

AF:

0.0000247

AC:

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

0.25

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.21

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.081

Eigen

Benign

0.18

Eigen_PC

Benign

0.099

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.97

M_CAP

Uncertain

0.10

MetaRNN

Benign

0.34

MetaSVM

Benign

-0.56

MutationAssessor

Pathogenic

3.1

PhyloP100

2.4

PrimateAI

Uncertain

0.72

PROVEAN

Pathogenic

-5.8

REVEL

Benign

0.25

Sift

Uncertain

0.028

Sift4G

Uncertain

0.021

Polyphen

0.80

Vest4

0.42

MutPred

0.48

Loss of disorder (P = 0.0419)

MVP

0.67

MPC

0.36

ClinPred

0.93

GERP RS

3.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.74

gMVP

0.47

Mutation Taster

=82/18

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over