3-139355961-AAC-A

Position:

• chr3-139355961-AAC-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_020191.4(MRPS22):​c.987+173_987+174delCA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0257 in 152,280 control chromosomes in the GnomAD database, including 79 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.026 (79 hom., cov: 32)
• Consequence: MRPS22 NM_020191.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.63

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 -10 ACMG points.

• BP6: Variant 3-139355961-AAC-A is Benign according to our data. Variant chr3-139355961-AAC-A is described in ClinVar as [Likely_benign]. Clinvar id is 1187892.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0257 (3919/152280) while in subpopulation SAS AF= 0.0352 (170/4824). AF 95% confidence interval is 0.0329. There are 79 homozygotes in gnomad4. There are 1899 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 79 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MRPS22	NM_020191.4	c.987+173_987+174delCA		intron_variant		ENST00000680020.1	NP_064576.1
MRPS22	NM_001363893.1	c.984+173_984+174delCA		intron_variant			NP_001350822.1
MRPS22	NM_001363857.1	c.864+173_864+174delCA		intron_variant			NP_001350786.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MRPS22	ENST00000680020.1	c.987+173_987+174delCA		intron_variant			NM_020191.4	ENSP00000505414.1

Frequencies

GnomAD3 genomes AF: 0.0257 AC: 3914 AN: 152162 Hom.: 78 Cov.: 32

Gnomad AFR AF: 0.00623

Gnomad AMI AF: 0.0484

Gnomad AMR AF: 0.0301

Gnomad ASJ AF: 0.0649

Gnomad EAS AF: 0.0202

Gnomad SAS AF: 0.0354

Gnomad FIN AF: 0.0253

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0341

Gnomad OTH AF: 0.0254

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

GnomAD4 genome AF: 0.0257 AC: 3919 AN: 152280 Hom.: 79 Cov.: 32 AF XY: 0.0255 AC XY: 1899 AN XY: 74450

Gnomad4 AFR AF: 0.00621

Gnomad4 AMR AF: 0.0301

Gnomad4 ASJ AF: 0.0649

Gnomad4 EAS AF: 0.0201

Gnomad4 SAS AF: 0.0352

Gnomad4 FIN AF: 0.0253

Gnomad4 NFE AF: 0.0341

Gnomad4 OTH AF: 0.0289

Alfa AF: 0.0264 Hom.: 8

Bravo AF: 0.0244

Asia WGS AF: 0.0360 AC: 125 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 27, 2020

- -

Computational scores

Source: dbNSFP v4.3

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: rs3830347; hg19: chr3-139074803;