Genetic Variant MRPL23:c.498-18125G>A (chr11-1993416-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001400176.1(MRPL23):c.498-18125G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.031 ( 983 hom., cov: 14)

Failed GnomAD Quality Control

Consequence

MRPL23
NM_001400176.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.513

Publications

14 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:

LINC01219 (HGNC:49653): (long intergenic non-protein coding RNA 1219)

LINC01219 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0576 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001400176.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRPL23	NM_001400176.1		c.498-18125G>A		intron	N/A	NP_001387105.1
	LINC01219	NR_126400.1		n.669G>A		non_coding_transcript_exon	Exon 3 of 3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank
LINC01219	ENST00000418612.3	TSL:2	n.775G>A	non_coding_transcript_exon	Exon 3 of 3
LINC01219	ENST00000733500.1		n.853G>A	non_coding_transcript_exon	Exon 4 of 4
LINC01219	ENST00000733501.1		n.817G>A	non_coding_transcript_exon	Exon 3 of 3

Frequencies

GnomAD3 genomes

AF:

0.0310

AC:

2636

AN:

85152

Hom.:

984

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00405

Gnomad AMI

AF:

0.00408

Gnomad AMR

AF:

0.0116

Gnomad ASJ

AF:

0.0299

Gnomad EAS

AF:

0.00477

Gnomad SAS

AF:

0.00894

Gnomad FIN

AF:

0.113

Gnomad MID

AF:

0.0169

Gnomad NFE

AF:

0.0600

Gnomad OTH

AF:

0.0150

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AC:

AN:

Hom.:

Cov.:

AC XY:

AN XY:

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AC:

AN:

Other (OTH)

AC:

AN:

GnomAD4 genome

AF:

0.0309

AC:

2634

AN:

85248

Hom.:

983

Cov.:

AF XY:

0.0318

AC XY:

1304

AN XY:

41010

show subpopulations

African (AFR)

AF:

0.00404

AC:

138

AN:

34188

American (AMR)

AF:

0.0116

AC:

AN:

8366

Ashkenazi Jewish (ASJ)

AF:

0.0299

AC:

AN:

1306

East Asian (EAS)

AF:

0.00478

AC:

AN:

2926

South Asian (SAS)

AF:

0.00897

AC:

AN:

2006

European-Finnish (FIN)

AF:

0.113

AC:

479

AN:

4248

Middle Eastern (MID)

AF:

0.0179

AC:

AN:

112

European-Non Finnish (NFE)

AF:

0.0599

AC:

1829

AN:

30534

Other (OTH)

AF:

0.0149

AC:

AN:

1072

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

122

153

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.452

Hom.:

45200

Asia WGS

AF:

0.279

AC:

971

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

6.9

(source)

DANN

Benign

0.69

PhyloP100

-0.51

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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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