Genetic Variant MRPL23:p.Asn23Lys (chr11-1950950-C-A) – 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.69C>A(p.Asn23Lys) 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: 5)

Exomes 𝑓: 0.000014 ( 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: 1.16

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 -1 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.32268733).

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.69C>A	p.Asn23Lys	missense	Exon 2 of 5	NP_066957.3
MRPL23	NM_001400176.1		c.69C>A	p.Asn23Lys	missense	Exon 2 of 7	NP_001387105.1
MRPL23	NM_001400179.1		c.69C>A	p.Asn23Lys	missense	Exon 2 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.69C>A	p.Asn23Lys	missense	Exon 2 of 5	ENSP00000380466.3	Q16540
MRPL23	ENST00000924183.1		c.69C>A	p.Asn23Lys	missense	Exon 2 of 5	ENSP00000594242.1
MRPL23	ENST00000397297.7	TSL:2	c.69C>A	p.Asn23Lys	missense	Exon 2 of 6	ENSP00000380465.3	A8MYK1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000798

AC:

AN:

250668

AF XY:

0.00000737

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000177

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000137

AC:

AN:

218958

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

113368

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

7044

American (AMR)

AF:

0.00

AC:

AN:

5858

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

6040

East Asian (EAS)

AF:

0.00

AC:

AN:

16326

South Asian (SAS)

AF:

0.00

AC:

AN:

16202

European-Finnish (FIN)

AF:

0.00

AC:

AN:

16366

Middle Eastern (MID)

AF:

0.00

AC:

AN:

936

European-Non Finnish (NFE)

AF:

0.0000219

AC:

AN:

137290

Other (OTH)

AF:

0.00

AC:

AN:

12896

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0000416442), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.358

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

Cov.:

ExAC

AF:

0.0000165

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

Pathogenic

0.72

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.45

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.14

Eigen

Benign

-0.20

Eigen_PC

Benign

-0.095

FATHMM_MKL

Benign

0.75

LIST_S2

Benign

0.79

M_CAP

Benign

0.0071

MetaRNN

Benign

0.32

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.7

PhyloP100

1.2

PrimateAI

Uncertain

0.74

PROVEAN

Uncertain

-4.3

REVEL

Benign

0.076

Sift

Benign

0.041

Sift4G

Benign

0.12

Polyphen

0.065

Vest4

0.46

MutPred

0.57

Gain of methylation at N23 (P = 0.0061)

MVP

0.39

MPC

0.20

ClinPred

0.67

GERP RS

3.5

Varity_R

0.67

gMVP

0.60

Mutation Taster

=78/22

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over