3-139307597-G-C

Variant names:

• chr3-139307597-G-C
• rs10935316
• ENST00000495075.5:c.-71-36359G>C

Variant summary

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

The ENST00000495075.5(MRPS22):​c.-71-36359G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.727 in 152,042 control chromosomes in the GnomAD database, including 41,205 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 0.73 (41205 hom., cov: 32)
• Consequence: MRPS22 ENST00000495075.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0480
• Publications: 6 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.829 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000495075.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRPS22	ENST00000495075.5	TSL:1	c.-71-36359G>C		intron	N/A	ENSP00000418008.1
	MRPS22	ENST00000688697.1		c.-72+24701G>C		intron	N/A	ENSP00000510396.1
	MRPS22	ENST00000687538.1		c.-39+24701G>C		intron	N/A	ENSP00000508887.1

Frequencies

GnomAD3 genomes AF: 0.727 AC: 110491 AN: 151924 Hom.: 41187 Cov.: 32

Gnomad AFR AF: 0.553

Gnomad AMI AF: 0.822

Gnomad AMR AF: 0.841

Gnomad ASJ AF: 0.822

Gnomad EAS AF: 0.607

Gnomad SAS AF: 0.827

Gnomad FIN AF: 0.767

Gnomad MID AF: 0.845

Gnomad NFE AF: 0.795

Gnomad OTH AF: 0.779

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

GnomAD4 genome AF: 0.727 AC: 110543 AN: 152042 Hom.: 41205 Cov.: 32 AF XY: 0.729 AC XY: 54185 AN XY: 74350

African (AFR) AF: 0.553 AC: 22902 AN: 41448

American (AMR) AF: 0.841 AC: 12863 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.822 AC: 2852 AN: 3470

East Asian (EAS) AF: 0.607 AC: 3131 AN: 5156

South Asian (SAS) AF: 0.828 AC: 3975 AN: 4802

European-Finnish (FIN) AF: 0.767 AC: 8113 AN: 10578

Middle Eastern (MID) AF: 0.857 AC: 252 AN: 294

European-Non Finnish (NFE) AF: 0.795 AC: 54060 AN: 67986

Other (OTH) AF: 0.780 AC: 1645 AN: 2108

Alfa AF: 0.687 Hom.: 2172

Bravo AF: 0.727

Asia WGS AF: 0.698 AC: 2430 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.1
DANN	Benign	0.60
PhyloP100		-0.048
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: rs10935316; hg19: chr3-139026439;