3-139354169-C-T

Position:

• chr3-139354169-C-T

Variant summary

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

The NM_020191.4(MRPS22):​c.878+1377C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.289 in 152,104 control chromosomes in the GnomAD database, including 7,669 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 0.29 (7669 hom., cov: 33)
• Consequence: MRPS22 NM_020191.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0990

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]

MRPS22 (HGNC:):

COPB2 (HGNC:2232): (COPI coat complex subunit beta 2) The Golgi coatomer complex (see MIM 601924) constitutes the coat of nonclathrin-coated vesicles and is essential for Golgi budding and vesicular trafficking. It consists of 7 protein subunits, including COPB2.[supplied by OMIM, Jul 2002]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.838 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MRPS22	NM_020191.4	c.878+1377C>T		intron_variant		ENST00000680020.1	NP_064576.1
MRPS22	NM_001363893.1	c.875+1377C>T		intron_variant			NP_001350822.1
MRPS22	NM_001363857.1	c.755+1377C>T		intron_variant			NP_001350786.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MRPS22	ENST00000680020.1	c.878+1377C>T		intron_variant			NM_020191.4	ENSP00000505414.1

Frequencies

GnomAD3 genomes AF: 0.289 AC: 43910 AN: 151986 Hom.: 7657 Cov.: 33

Gnomad AFR AF: 0.249

Gnomad AMI AF: 0.145

Gnomad AMR AF: 0.455

Gnomad ASJ AF: 0.210

Gnomad EAS AF: 0.859

Gnomad SAS AF: 0.304

Gnomad FIN AF: 0.262

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.242

Gnomad OTH AF: 0.277

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

GnomAD4 genome AF: 0.289 AC: 43951 AN: 152104 Hom.: 7669 Cov.: 33 AF XY: 0.295 AC XY: 21969 AN XY: 74366

Gnomad4 AFR AF: 0.249

Gnomad4 AMR AF: 0.456

Gnomad4 ASJ AF: 0.210

Gnomad4 EAS AF: 0.859

Gnomad4 SAS AF: 0.304

Gnomad4 FIN AF: 0.262

Gnomad4 NFE AF: 0.242

Gnomad4 OTH AF: 0.277

Alfa AF: 0.245 Hom.: 4621

Bravo AF: 0.308

Asia WGS AF: 0.523 AC: 1815 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	7.4
DANN	Benign	0.57

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: rs1044826; hg19: chr3-139073011;