rs9289573

Positions:

• chr3-139341880-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000495075.5(MRPS22):​c.-71-2076C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.669 in 152,084 control chromosomes in the GnomAD database, including 36,932 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 0.67 (36932 hom., cov: 32)
• Consequence: MRPS22 ENST00000495075.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.85

Genes affected

MRPS22 (HGNC:14508): (mitochondrial ribosomal protein S22) 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 that does not seem to have a counterpart in prokaryotic and fungal-mitochondrial ribosomes. This gene lies telomeric of and is transcribed in the opposite direction from the forkhead box L2 gene. A pseudogene corresponding to this gene is found on chromosome Xq. [provided by RefSeq, Jul 2008]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.883 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.139341880C>T		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MRPS22	ENST00000495075.5	c.-71-2076C>T		intron_variant		1		ENSP00000418008.1
MRPS22	ENST00000688697.1	c.-71-2076C>T		intron_variant				ENSP00000510396.1
MRPS22	ENST00000687538.1	c.-38-4998C>T		intron_variant				ENSP00000508887.1

Frequencies

GnomAD3 genomes AF: 0.670 AC: 101743 AN: 151966 Hom.: 36922 Cov.: 32

Gnomad AFR AF: 0.356

Gnomad AMI AF: 0.841

Gnomad AMR AF: 0.792

Gnomad ASJ AF: 0.710

Gnomad EAS AF: 0.904

Gnomad SAS AF: 0.715

Gnomad FIN AF: 0.817

Gnomad MID AF: 0.656

Gnomad NFE AF: 0.783

Gnomad OTH AF: 0.700

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.669 AC: 101777 AN: 152084 Hom.: 36932 Cov.: 32 AF XY: 0.674 AC XY: 50090 AN XY: 74348

Gnomad4 AFR AF: 0.356

Gnomad4 AMR AF: 0.792

Gnomad4 ASJ AF: 0.710

Gnomad4 EAS AF: 0.904

Gnomad4 SAS AF: 0.717

Gnomad4 FIN AF: 0.817

Gnomad4 NFE AF: 0.783

Gnomad4 OTH AF: 0.700

Alfa AF: 0.744 Hom.: 17514

Bravo AF: 0.656

Asia WGS AF: 0.766 AC: 2664 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	14
DANN	Benign	0.82

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: rs9289573; hg19: chr3-139060722;