3-139302297-T-C

Variant names:

• chr3-139302297-T-C
• rs4894405
• ENST00000495075.5:c.-71-41659T>C

Variant summary

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

The ENST00000495075.5(MRPS22):​c.-71-41659T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.698 in 152,024 control chromosomes in the GnomAD database, including 37,658 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 0.70 (37658 hom., cov: 32)
• Consequence: MRPS22 ENST00000495075.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.39
• Publications: 7 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: Orphanet, Labcorp Genetics (formerly Invitae), 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.738 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRPS22	ENST00000495075.5	TSL:1	c.-71-41659T>C		intron	N/A	ENSP00000418008.1	P82650-1
	MRPS22	ENST00000688697.1		c.-72+19401T>C		intron	N/A	ENSP00000510396.1	P82650-1
	MRPS22	ENST00000687538.1		c.-39+19401T>C		intron	N/A	ENSP00000508887.1	G5E9W7

Frequencies

GnomAD3 genomes AF: 0.698 AC: 106066 AN: 151906 Hom.: 37626 Cov.: 32

Gnomad AFR AF: 0.744

Gnomad AMI AF: 0.841

Gnomad AMR AF: 0.514

Gnomad ASJ AF: 0.773

Gnomad EAS AF: 0.560

Gnomad SAS AF: 0.617

Gnomad FIN AF: 0.702

Gnomad MID AF: 0.729

Gnomad NFE AF: 0.722

Gnomad OTH AF: 0.680

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

GnomAD4 genome AF: 0.698 AC: 106141 AN: 152024 Hom.: 37658 Cov.: 32 AF XY: 0.693 AC XY: 51490 AN XY: 74328

African (AFR) AF: 0.745 AC: 30871 AN: 41458

American (AMR) AF: 0.513 AC: 7832 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.773 AC: 2682 AN: 3470

East Asian (EAS) AF: 0.559 AC: 2887 AN: 5160

South Asian (SAS) AF: 0.616 AC: 2966 AN: 4816

European-Finnish (FIN) AF: 0.702 AC: 7427 AN: 10578

Middle Eastern (MID) AF: 0.723 AC: 211 AN: 292

European-Non Finnish (NFE) AF: 0.722 AC: 49075 AN: 67956

Other (OTH) AF: 0.676 AC: 1425 AN: 2108

Alfa AF: 0.707 Hom.: 123019

Bravo AF: 0.682

Asia WGS AF: 0.583 AC: 2032 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.30
DANN	Benign	0.43
PhyloP100		-1.4
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs4894405;

hg19: chr3-139021139;