rs955084

Variant names:

• chr3-139203253-A-G
• rs955084
• ENST00000495075.5:c.-72+22893A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000495075.5(MRPS22):​c.-72+22893A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.202 in 152,136 control chromosomes in the GnomAD database, including 4,032 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 0.20 (4032 hom., cov: 32)
• Consequence: MRPS22 ENST00000495075.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.79
• Publications: 1 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]

MRPS22 Gene-Disease associations (from GenCC):

• mitochondrial disease

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• hypotonia with lactic acidemia and hyperammonemia

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, G2P
• 46 XX gonadal dysgenesis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• ovarian dysgenesis 7

  Inheritance: AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.288 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.-72+22893A>G		intron_variant	Intron 2 of 9	1		ENSP00000418008.1
MRPS22	ENST00000495225.1	n.459+40043A>G		intron_variant	Intron 3 of 3	3

Frequencies

GnomAD3 genomes AF: 0.203 AC: 30791 AN: 152018 Hom.: 4034 Cov.: 32

Gnomad AFR AF: 0.0573

Gnomad AMI AF: 0.366

Gnomad AMR AF: 0.195

Gnomad ASJ AF: 0.267

Gnomad EAS AF: 0.0278

Gnomad SAS AF: 0.277

Gnomad FIN AF: 0.221

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.291

Gnomad OTH AF: 0.226

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

GnomAD4 genome AF: 0.202 AC: 30789 AN: 152136 Hom.: 4032 Cov.: 32 AF XY: 0.198 AC XY: 14691 AN XY: 74364

African (AFR) AF: 0.0571 AC: 2371 AN: 41512

American (AMR) AF: 0.194 AC: 2971 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.267 AC: 926 AN: 3472

East Asian (EAS) AF: 0.0278 AC: 144 AN: 5174

South Asian (SAS) AF: 0.277 AC: 1335 AN: 4816

European-Finnish (FIN) AF: 0.221 AC: 2338 AN: 10586

Middle Eastern (MID) AF: 0.279 AC: 82 AN: 294

European-Non Finnish (NFE) AF: 0.291 AC: 19810 AN: 67982

Other (OTH) AF: 0.228 AC: 480 AN: 2106

Alfa AF: 0.229 Hom.: 602

Bravo AF: 0.189

Asia WGS AF: 0.146 AC: 510 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.26
DANN	Benign	0.53
PhyloP100		-1.8
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: rs955084; hg19: chr3-138922095;