17-57839280-G-T

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
MRPS23	NM_016070.4	c.*503C>A		3_prime_UTR_variant	5/5	ENST00000313608.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MRPS23	ENST00000313608.13	c.*503C>A		3_prime_UTR_variant	5/5	1	NM_016070.4	P1

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

Gnomad4 AFR exome AF: 0.500

Gnomad4 AMR exome AF: 0.653

Gnomad4 ASJ exome AF: 0.500

Gnomad4 EAS exome AF: 0.767

Gnomad4 SAS exome AF: 0.818

Gnomad4 FIN exome AF: 0.375

Gnomad4 NFE exome AF: 0.559

Gnomad4 OTH exome AF: 0.625

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

Gnomad4 AFR AF: 0.533

Gnomad4 AMR AF: 0.608

Gnomad4 ASJ AF: 0.636

Gnomad4 EAS AF: 0.793

Gnomad4 SAS AF: 0.782

Gnomad4 FIN AF: 0.528

Gnomad4 NFE AF: 0.542

Gnomad4 OTH AF: 0.590

Alfa AF: 0.557 Hom.: 34017

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
Dann	Benign	0.81

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

LitVar

Other links and lift over

dbSNP: rs2586038; hg19: chr17-55916641;