3-139354169-C-T

Variant names:

• chr3-139354169-C-T
• rs1044826
• NM_020191.4:c.878+1377C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 13 publications found

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]

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]

COPB2 Gene-Disease associations (from GenCC):

• osteoporosis, childhood- or juvenile-onset, with developmental delay

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
• autosomal recessive primary microcephaly

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• microcephaly 19, primary, autosomal recessive

  Inheritance: AR, Unknown Classification: LIMITED Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020191.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRPS22	NM_020191.4	MANE Select	c.878+1377C>T		intron	N/A	NP_064576.1	P82650-1
	MRPS22	NM_001363893.1		c.875+1377C>T		intron	N/A	NP_001350822.1	A0A7P0MKV3
	MRPS22	NM_001363857.1		c.755+1377C>T		intron	N/A	NP_001350786.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRPS22	ENST00000680020.1	MANE Select	c.878+1377C>T		intron	N/A	ENSP00000505414.1	P82650-1
	MRPS22	ENST00000495075.5	TSL:1	c.878+1377C>T		intron	N/A	ENSP00000418008.1	P82650-1
	MRPS22	ENST00000310776.9	TSL:1	c.875+1377C>T		intron	N/A	ENSP00000310785.5	A0A7P0MKV3

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

African (AFR) AF: 0.249 AC: 10349 AN: 41502

American (AMR) AF: 0.456 AC: 6963 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.210 AC: 730 AN: 3470

East Asian (EAS) AF: 0.859 AC: 4438 AN: 5166

South Asian (SAS) AF: 0.304 AC: 1465 AN: 4816

European-Finnish (FIN) AF: 0.262 AC: 2772 AN: 10570

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.242 AC: 16472 AN: 67998

Other (OTH) AF: 0.277 AC: 584 AN: 2112

Alfa AF: 0.265 Hom.: 10040

Bravo AF: 0.308

Asia WGS AF: 0.523 AC: 1815 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	7.4
DANN	Benign	0.57
PhyloP100		-0.099
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1044826; hg19: chr3-139073011;