ENST00000495075.5:c.-72+29005G>A

Variant names:

• chr3-139209365-G-A
• rs1521558
• ENST00000495075.5:c.-72+29005G>A

Variant summary

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

The ENST00000495075.5(MRPS22):​c.-72+29005G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.33 in 151,928 control chromosomes in the GnomAD database, including 8,627 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 0.33 (8627 hom., cov: 32)
• Consequence: MRPS22 ENST00000495075.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.327
• Publications: 4 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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.622 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+29005G>A		intron_variant	Intron 2 of 9	1		ENSP00000418008.1
MRPS22	ENST00000495225.1	n.459+46155G>A		intron_variant	Intron 3 of 3	3

Frequencies

GnomAD3 genomes AF: 0.330 AC: 50034 AN: 151810 Hom.: 8627 Cov.: 32

Gnomad AFR AF: 0.327

Gnomad AMI AF: 0.326

Gnomad AMR AF: 0.386

Gnomad ASJ AF: 0.343

Gnomad EAS AF: 0.641

Gnomad SAS AF: 0.324

Gnomad FIN AF: 0.322

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.296

Gnomad OTH AF: 0.319

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

GnomAD4 genome AF: 0.330 AC: 50063 AN: 151928 Hom.: 8627 Cov.: 32 AF XY: 0.334 AC XY: 24826 AN XY: 74258

African (AFR) AF: 0.328 AC: 13570 AN: 41430

American (AMR) AF: 0.386 AC: 5886 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.343 AC: 1188 AN: 3468

East Asian (EAS) AF: 0.640 AC: 3304 AN: 5162

South Asian (SAS) AF: 0.323 AC: 1554 AN: 4818

European-Finnish (FIN) AF: 0.322 AC: 3396 AN: 10554

Middle Eastern (MID) AF: 0.241 AC: 71 AN: 294

European-Non Finnish (NFE) AF: 0.296 AC: 20130 AN: 67922

Other (OTH) AF: 0.316 AC: 667 AN: 2110

Alfa AF: 0.313 Hom.: 32106

Bravo AF: 0.340

Asia WGS AF: 0.453 AC: 1570 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.9
DANN	Benign	0.66
PhyloP100		-0.33
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: rs1521558; hg19: chr3-138928207;