17-57839930-G-A

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_016070.4(MRPS23):c.426C>T(p.His142=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00671 in 1,614,046 control chromosomes in the GnomAD database, including 60 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0049 (3 hom., cov: 33)
  • Exomes 𝑓: 0.0069 (57 hom.)
• Consequence: MRPS23 NM_016070.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.299

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 -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 17-57839930-G-A is Benign according to our data. Variant chr17-57839930-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 778718.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.299 with no splicing effect.
• BS2: High Homozygotes in GnomAd at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MRPS23	NM_016070.4	c.426C>T	p.His142=	synonymous_variant	5/5	ENST00000313608.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MRPS23	ENST00000313608.13	c.426C>T	p.His142=	synonymous_variant	5/5	1	NM_016070.4	P1

Frequencies

GnomAD3 genomes AF: 0.00489 AC: 744 AN: 152142 Hom.: 3 Cov.: 33

Gnomad AFR AF: 0.00188

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00255

Gnomad ASJ AF: 0.00461

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00189

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00850

Gnomad OTH AF: 0.00525

GnomAD3 exomes AF: 0.00432 AC: 1087 AN: 251428 Hom.: 5 AF XY: 0.00430 AC XY: 584 AN XY: 135892

Gnomad AFR exome AF: 0.00148

Gnomad AMR exome AF: 0.00130

Gnomad ASJ exome AF: 0.00665

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000425

Gnomad FIN exome AF: 0.00222

Gnomad NFE exome AF: 0.00756

Gnomad OTH exome AF: 0.00489

GnomAD4 exome AF: 0.00690 AC: 10091 AN: 1461786 Hom.: 57 Cov.: 30 AF XY: 0.00680 AC XY: 4945 AN XY: 727182

Gnomad4 AFR exome AF: 0.00137

Gnomad4 AMR exome AF: 0.00150

Gnomad4 ASJ exome AF: 0.00612

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000464

Gnomad4 FIN exome AF: 0.00311

Gnomad4 NFE exome AF: 0.00836

Gnomad4 OTH exome AF: 0.00530

GnomAD4 genome AF: 0.00489 AC: 744 AN: 152260 Hom.: 3 Cov.: 33 AF XY: 0.00431 AC XY: 321 AN XY: 74434

Gnomad4 AFR AF: 0.00188

Gnomad4 AMR AF: 0.00255

Gnomad4 ASJ AF: 0.00461

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00189

Gnomad4 NFE AF: 0.00850

Gnomad4 OTH AF: 0.00520

Alfa AF: 0.00681 Hom.: 3

Bravo AF: 0.00468

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00703

EpiControl AF: 0.00723

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 22, 2024	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Feb 01, 2024	MRPS23: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	6.3
Dann	Benign	0.52
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs117066436; hg19: chr17-55917291;