rs9289573

Variant names:

• chr3-139341880-C-T
• rs9289573
• ENST00000495075.5:c.-71-2076C>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]

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 rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MRPS22	ENST00000495075.5	c.-71-2076C>T		intron_variant	Intron 2 of 9	1		ENSP00000418008.1
MRPS22	ENST00000688697.1	c.-71-2076C>T		intron_variant	Intron 2 of 9			ENSP00000510396.1
MRPS22	ENST00000687538.1	c.-38-4998C>T		intron_variant	Intron 2 of 8			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;