17-57839280-G-T

Variant names:

• chr17-57839280-G-T
• rs2586038
• NM_016070.4:c.*503C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.412
• Publications: 12 publications found

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)

ACMG classification

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016070.4. 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
	MRPS23	NM_016070.4	MANE Select	c.*503C>A		3_prime_UTR	Exon 5 of 5	NP_057154.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRPS23	ENST00000313608.13	TSL:1 MANE Select	c.*503C>A		3_prime_UTR	Exon 5 of 5	ENSP00000320184.8
	MRPS23	ENST00000916567.1		c.*503C>A		downstream_gene	N/A	ENSP00000586626.1
	MRPS23	ENST00000916566.1		c.*503C>A		downstream_gene	N/A	ENSP00000586625.1

Frequencies

GnomAD3 genomes AF: 0.565 AC: 85769 AN: 151902 Hom.: 24467 Cov.: 33

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.: 0 AF XY: 0.581 AC XY: 243 AN XY: 418

African (AFR) AF: 0.500 AC: 1 AN: 2

American (AMR) AF: 0.653 AC: 98 AN: 150

Ashkenazi Jewish (ASJ) AF: 0.500 AC: 1 AN: 2

East Asian (EAS) AF: 0.767 AC: 23 AN: 30

South Asian (SAS) AF: 0.818 AC: 36 AN: 44

European-Finnish (FIN) AF: 0.375 AC: 3 AN: 8

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.559 AC: 342 AN: 612

Other (OTH) AF: 0.625 AC: 15 AN: 24

GnomAD4 genome AF: 0.564 AC: 85814 AN: 152020 Hom.: 24478 Cov.: 33 AF XY: 0.570 AC XY: 42360 AN XY: 74300

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

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	0.75
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

Other links and lift over

dbSNP: rs2586038; hg19: chr17-55916641;