Genetic Variant MRPS23:c.*503C>A (chr17-57839280-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_016070.4(MRPS23):c.*503C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.565 in 152,892 control chromosomes in the GnomAD database, including 24,639 homozygotes. 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 0.56 ( 24478 hom., cov: 33)

Exomes 𝑓: 0.60 ( 161 hom. )

Consequence

MRPS23
NM_016070.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.412

Publications

12 publications found

Variant links:

Genes affected

MRPS23 (HGNC:14509): (mitochondrial ribosomal protein S23) 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 28S subunit protein. A pseudogene corresponding to this gene is found on chromosome 7p. [provided by RefSeq, Jul 2008]

MRPS23 Gene-Disease associations (from GenCC):

combined oxidative phosphorylation deficiency 46
Inheritance: AR, Unknown Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

MRPS23 links:

Genome browser will be placed here

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=-0.74).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.772 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MRPS23	NM_016070.4 link	c.*503C>A		3_prime_UTR_variant	Exon 5 of 5	ENST00000313608.13	NP_057154.2	Q9Y3D9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MRPS23	ENST00000313608.13 link	c.*503C>A		3_prime_UTR_variant	Exon 5 of 5	1	NM_016070.4	ENSP00000320184.8		Q9Y3D9

Frequencies

GnomAD3 genomes

AF:

0.565

AC:

85769

AN:

151902

Hom.:

24467

Cov.:

show subpopulations

Gnomad AFR

AF:

0.533

Gnomad AMI

AF:

0.586

Gnomad AMR

AF:

0.608

Gnomad ASJ

AF:

0.636

Gnomad EAS

AF:

0.793

Gnomad SAS

AF:

0.782

Gnomad FIN

AF:

0.528

Gnomad MID

AF:

0.649

Gnomad NFE

AF:

0.542

Gnomad OTH

AF:

0.590

GnomAD4 exome

AF:

0.595

AC:

519

AN:

872

Hom.:

161

Cov.:

AF XY:

0.581

AC XY:

243

AN XY:

418

show subpopulations

African (AFR)

AF:

0.500

AC:

AN:

American (AMR)

AF:

0.653

AC:

AN:

150

Ashkenazi Jewish (ASJ)

AF:

0.500

AC:

AN:

East Asian (EAS)

AF:

0.767

AC:

AN:

South Asian (SAS)

AF:

0.818

AC:

AN:

European-Finnish (FIN)

AF:

0.375

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.559

AC:

342

AN:

612

Other (OTH)

AF:

0.625

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.518

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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

AF:

0.564

AC:

85814

AN:

152020

Hom.:

24478

Cov.:

AF XY:

0.570

AC XY:

42360

AN XY:

74300

show subpopulations

African (AFR)

AF:

0.533

AC:

22077

AN:

41450

American (AMR)

AF:

0.608

AC:

9292

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.636

AC:

2209

AN:

3472

East Asian (EAS)

AF:

0.793

AC:

4093

AN:

5164

South Asian (SAS)

AF:

0.782

AC:

3774

AN:

4826

European-Finnish (FIN)

AF:

0.528

AC:

5557

AN:

10530

Middle Eastern (MID)

AF:

0.636

AC:

187

AN:

294

European-Non Finnish (NFE)

AF:

0.542

AC:

36846

AN:

67980

Other (OTH)

AF:

0.590

AC:

1247

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1956

3912

5869

7825

9781

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

754

1508

2262

3016

3770

<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:

0.557

Hom.:

55313

Bravo

AF:

0.569

Asia WGS

AF:

0.760

AC:

2645

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

0.75

(source)

DANN

Benign

0.81

PhyloP100

-0.41

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over