rs4243399

Variant names:

• chr3-139332068-G-A
• rs4243399
• ENST00000495075.5:c.-71-11888G>A

Your query was ambiguous. Multiple possible variants found:

• chr3-139332068-G-A
• chr3-139332068-G-C

Variant summary

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

The ENST00000495075.5(MRPS22):​c.-71-11888G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.888 in 152,246 control chromosomes in the GnomAD database, including 60,900 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 0.89 (60900 hom., cov: 32)
• Consequence: MRPS22 ENST00000495075.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.384
• Publications: 5 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: G2P, Labcorp Genetics (formerly Invitae), Orphanet
• 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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.951 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.-71-11888G>A		intron	N/A	ENSP00000418008.1	P82650-1
	MRPS22	ENST00000688697.1		c.-71-11888G>A		intron	N/A	ENSP00000510396.1	P82650-1
	MRPS22	ENST00000687538.1		c.-38-14810G>A		intron	N/A	ENSP00000508887.1	G5E9W7

Frequencies

GnomAD3 genomes AF: 0.888 AC: 135113 AN: 152128 Hom.: 60869 Cov.: 32

Gnomad AFR AF: 0.724

Gnomad AMI AF: 0.951

Gnomad AMR AF: 0.928

Gnomad ASJ AF: 0.896

Gnomad EAS AF: 0.972

Gnomad SAS AF: 0.894

Gnomad FIN AF: 0.974

Gnomad MID AF: 0.914

Gnomad NFE AF: 0.957

Gnomad OTH AF: 0.902

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

GnomAD4 genome AF: 0.888 AC: 135192 AN: 152246 Hom.: 60900 Cov.: 32 AF XY: 0.891 AC XY: 66319 AN XY: 74450

African (AFR) AF: 0.723 AC: 30019 AN: 41492

American (AMR) AF: 0.929 AC: 14198 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.896 AC: 3111 AN: 3472

East Asian (EAS) AF: 0.972 AC: 5035 AN: 5178

South Asian (SAS) AF: 0.895 AC: 4321 AN: 4828

European-Finnish (FIN) AF: 0.974 AC: 10344 AN: 10622

Middle Eastern (MID) AF: 0.908 AC: 265 AN: 292

European-Non Finnish (NFE) AF: 0.957 AC: 65130 AN: 68046

Other (OTH) AF: 0.900 AC: 1902 AN: 2114

Alfa AF: 0.917 Hom.: 21161

Bravo AF: 0.879

Asia WGS AF: 0.908 AC: 3158 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	2.5
DANN	Benign	0.56
PhyloP100		-0.38
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: rs4243399;

hg19: chr3-139050910;