chr3-139197551-C-T

Variant names:

• chr3-139197551-C-T
• rs11706018
• ENST00000495075.5:c.-72+17191C>T

Variant summary

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

The ENST00000495075.5(MRPS22):​c.-72+17191C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.143 in 152,010 control chromosomes in the GnomAD database, including 2,256 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 0.14 (2256 hom., cov: 32)
• Consequence: MRPS22 ENST00000495075.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.145
• Publications: 6 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)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.358 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MRPS22	ENST00000495075.5	c.-72+17191C>T		intron_variant	Intron 2 of 9	1		ENSP00000418008.1
MRPS22	ENST00000495225.1	n.459+34341C>T		intron_variant	Intron 3 of 3	3

Frequencies

GnomAD3 genomes AF: 0.143 AC: 21739 AN: 151892 Hom.: 2251 Cov.: 32

Gnomad AFR AF: 0.270

Gnomad AMI AF: 0.0789

Gnomad AMR AF: 0.0865

Gnomad ASJ AF: 0.0827

Gnomad EAS AF: 0.373

Gnomad SAS AF: 0.0374

Gnomad FIN AF: 0.0884

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0824

Gnomad OTH AF: 0.112

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

GnomAD4 genome AF: 0.143 AC: 21768 AN: 152010 Hom.: 2256 Cov.: 32 AF XY: 0.142 AC XY: 10517 AN XY: 74280

African (AFR) AF: 0.270 AC: 11201 AN: 41440

American (AMR) AF: 0.0864 AC: 1320 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0827 AC: 287 AN: 3470

East Asian (EAS) AF: 0.372 AC: 1918 AN: 5154

South Asian (SAS) AF: 0.0368 AC: 177 AN: 4814

European-Finnish (FIN) AF: 0.0884 AC: 933 AN: 10554

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.0824 AC: 5603 AN: 67982

Other (OTH) AF: 0.110 AC: 233 AN: 2110

Alfa AF: 0.101 Hom.: 4661

Bravo AF: 0.151

Asia WGS AF: 0.165 AC: 573 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.9
DANN	Benign	0.58
PhyloP100		0.14
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: rs11706018; hg19: chr3-138916393;