MRPS22 p.Ile95Leu

Variant names:

• chr3-139346988-A-T
• NM_020191.4:c.283A>T
• MRPS22 p.Ile95Leu

Your query was ambiguous. Multiple possible variants found:

• chr3-139346988-A-T
• chr3-139346988-A-C
• chr3-139346988-ATA-TTG
• chr3-139346988-ATA-CTT
• chr3-139346988-ATA-CTC
• chr3-139346988-ATA-CTG

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_020191.4(MRPS22):​c.283A>T​(p.Ile95Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Benign in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I95V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MRPS22 NM_020191.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.359
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.03941998).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020191.4. 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
	MRPS22	NM_020191.4	MANE Select	c.283A>T	p.Ile95Leu	missense	Exon 2 of 8	NP_064576.1	P82650-1
	MRPS22	NM_001363893.1		c.280A>T	p.Ile94Leu	missense	Exon 2 of 8	NP_001350822.1	A0A7P0MKV3
	MRPS22	NM_001363857.1		c.160A>T	p.Ile54Leu	missense	Exon 2 of 8	NP_001350786.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRPS22	ENST00000680020.1	MANE Select	c.283A>T	p.Ile95Leu	missense	Exon 2 of 8	ENSP00000505414.1	P82650-1
	MRPS22	ENST00000495075.5	TSL:1	c.283A>T	p.Ile95Leu	missense	Exon 4 of 10	ENSP00000418008.1	P82650-1
	MRPS22	ENST00000310776.9	TSL:1	c.280A>T	p.Ile94Leu	missense	Exon 2 of 8	ENSP00000310785.5	A0A7P0MKV3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	0.011
DANN	Benign	0.72
DEOGEN2	Benign	0.19	T
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.076	N
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.039	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.34	N
PhyloP100		-0.36
PrimateAI	Benign	0.27	T
PROVEAN	Benign	0.23	N
REVEL	Benign	0.20
Sift	Benign	0.46	T
Sift4G	Benign	0.37	T
Varity_R		0.041
gMVP		0.22
Mutation Taster		=98/2	polymorphism

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

hg19: chr3-139065830;