3-139326219-T-G

Variant names:

• chr3-139326219-T-G
• rs1873668
• ENST00000495075.5:c.-71-17737T>G

Variant summary

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

The ENST00000495075.5(MRPS22):​c.-71-17737T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.905 in 152,198 control chromosomes in the GnomAD database, including 62,947 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 0.91 (62947 hom., cov: 31)
• Consequence: MRPS22 ENST00000495075.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.130
• 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: 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)

LOC124909439 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.954 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.-71-17737T>G		intron	N/A	ENSP00000418008.1	P82650-1
	MRPS22	ENST00000688697.1		c.-71-17737T>G		intron	N/A	ENSP00000510396.1	P82650-1
	MRPS22	ENST00000687538.1		c.-38-20659T>G		intron	N/A	ENSP00000508887.1	G5E9W7

Frequencies

GnomAD3 genomes AF: 0.905 AC: 137694 AN: 152080 Hom.: 62909 Cov.: 31

Gnomad AFR AF: 0.774

Gnomad AMI AF: 0.951

Gnomad AMR AF: 0.940

Gnomad ASJ AF: 0.916

Gnomad EAS AF: 0.975

Gnomad SAS AF: 0.904

Gnomad FIN AF: 0.974

Gnomad MID AF: 0.934

Gnomad NFE AF: 0.960

Gnomad OTH AF: 0.917

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

GnomAD4 genome AF: 0.905 AC: 137785 AN: 152198 Hom.: 62947 Cov.: 31 AF XY: 0.907 AC XY: 67542 AN XY: 74430

African (AFR) AF: 0.774 AC: 32098 AN: 41486

American (AMR) AF: 0.940 AC: 14372 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.916 AC: 3181 AN: 3472

East Asian (EAS) AF: 0.975 AC: 5035 AN: 5162

South Asian (SAS) AF: 0.905 AC: 4365 AN: 4824

European-Finnish (FIN) AF: 0.974 AC: 10348 AN: 10622

Middle Eastern (MID) AF: 0.929 AC: 273 AN: 294

European-Non Finnish (NFE) AF: 0.960 AC: 65316 AN: 68020

Other (OTH) AF: 0.915 AC: 1932 AN: 2112

Alfa AF: 0.923 Hom.: 10366

Bravo AF: 0.898

Asia WGS AF: 0.916 AC: 3187 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.5
DANN	Benign	0.68
PhyloP100		-0.13
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: rs1873668;

hg19: chr3-139045061;