3-139324394-C-G

Variant names:

• chr3-139324394-C-G
• rs4894410
• ENST00000495075.5:c.-71-19562C>G

Variant summary

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

The ENST00000495075.5(MRPS22):​c.-71-19562C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.928 in 152,186 control chromosomes in the GnomAD database, including 65,754 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 0.93 (65754 hom., cov: 31)
• Consequence: MRPS22 ENST00000495075.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.834
• 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: 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)

ENSG00000286988 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.956 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC124909439	XM_047449421.1	c.130-7490G>C		intron_variant	Intron 1 of 1		XP_047305377.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MRPS22	ENST00000495075.5	c.-71-19562C>G		intron_variant	Intron 2 of 9	1		ENSP00000418008.1
MRPS22	ENST00000688697.1	c.-71-19562C>G		intron_variant	Intron 2 of 9			ENSP00000510396.1
MRPS22	ENST00000687538.1	c.-38-22484C>G		intron_variant	Intron 2 of 8			ENSP00000508887.1

Frequencies

GnomAD3 genomes AF: 0.928 AC: 141183 AN: 152068 Hom.: 65717 Cov.: 31

Gnomad AFR AF: 0.864

Gnomad AMI AF: 0.952

Gnomad AMR AF: 0.943

Gnomad ASJ AF: 0.925

Gnomad EAS AF: 0.978

Gnomad SAS AF: 0.955

Gnomad FIN AF: 0.974

Gnomad MID AF: 0.918

Gnomad NFE AF: 0.951

Gnomad OTH AF: 0.938

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

GnomAD4 genome AF: 0.928 AC: 141276 AN: 152186 Hom.: 65754 Cov.: 31 AF XY: 0.930 AC XY: 69238 AN XY: 74412

African (AFR) AF: 0.864 AC: 35831 AN: 41484

American (AMR) AF: 0.943 AC: 14429 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.925 AC: 3212 AN: 3472

East Asian (EAS) AF: 0.978 AC: 5037 AN: 5148

South Asian (SAS) AF: 0.956 AC: 4604 AN: 4816

European-Finnish (FIN) AF: 0.974 AC: 10334 AN: 10612

Middle Eastern (MID) AF: 0.915 AC: 269 AN: 294

European-Non Finnish (NFE) AF: 0.951 AC: 64712 AN: 68034

Other (OTH) AF: 0.936 AC: 1980 AN: 2116

Alfa AF: 0.942 Hom.: 7888

Bravo AF: 0.924

Asia WGS AF: 0.947 AC: 3294 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.50
DANN	Benign	0.33
PhyloP100		-0.83
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: rs4894410; hg19: chr3-139043236;