dbSNP rs149980789: MRPL23:p.Thr106Lys (chr11-1956275-C-A) – 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.317C>A(p.Thr106Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict 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. T106M) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 18)

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: 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:

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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=0.01553607).

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>A	p.Thr106Lys	missense	Exon 5 of 5	NP_066957.3
MRPL23	NM_001400172.1		c.182C>A	p.Thr61Lys	missense	Exon 5 of 5	NP_001387101.1
MRPL23	NM_001400174.1		c.*52C>A		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>A	p.Thr106Lys	missense	Exon 5 of 5	ENSP00000380466.3	Q16540
MRPL23	ENST00000924183.1		c.473C>A	p.Thr158Lys	missense	Exon 5 of 5	ENSP00000594242.1
MRPL23	ENST00000869798.1		c.323C>A	p.Thr108Lys	missense	Exon 5 of 5	ENSP00000539857.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.000172

AC:

AN:

250230

AF XY:

0.000103

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00125

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

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

AF:

0.00

AC:

AN:

1383572

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

687638

African (AFR)

AF:

0.00

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:

0.00

AC:

AN:

1065410

Other (OTH)

AF:

0.00

AC:

AN:

57020

GnomAD4 genome

Cov.:

ExAC

AF:

0.000165

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

0.11

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.57

CADD

Benign

(source)

DANN

Benign

0.90

DEOGEN2

Benign

0.0015

Eigen

Benign

-0.53

Eigen_PC

Benign

-0.34

FATHMM_MKL

Benign

0.54

LIST_S2

Uncertain

0.89

M_CAP

Benign

0.016

MetaRNN

Benign

0.016

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.075

PhyloP100

0.46

PrimateAI

Uncertain

0.57

PROVEAN

Benign

-0.76

REVEL

Benign

0.034

Sift

Benign

0.61

Sift4G

Benign

0.81

Polyphen

0.087

Vest4

0.14

MutPred

0.42

Gain of methylation at T106 (P = 3e-04)

MVP

0.33

MPC

0.27

ClinPred

0.052

GERP RS

3.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.33

gMVP

0.33

Mutation Taster

=85/15

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