3-139307683-A-C

Variant names:

• chr3-139307683-A-C
• rs10935317
• ENST00000495075.5:c.-71-36273A>C

Variant summary

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

The ENST00000495075.5(MRPS22):​c.-71-36273A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.428 in 151,902 control chromosomes in the GnomAD database, including 14,422 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 0.43 (14422 hom., cov: 32)
• Consequence: MRPS22 ENST00000495075.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.249
• 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)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.563 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRPS22	ENST00000495075.5	TSL:1	c.-71-36273A>C		intron	N/A	ENSP00000418008.1
	MRPS22	ENST00000688697.1		c.-72+24787A>C		intron	N/A	ENSP00000510396.1
	MRPS22	ENST00000687538.1		c.-39+24787A>C		intron	N/A	ENSP00000508887.1

Frequencies

GnomAD3 genomes AF: 0.428 AC: 64918 AN: 151784 Hom.: 14405 Cov.: 32

Gnomad AFR AF: 0.384

Gnomad AMI AF: 0.407

Gnomad AMR AF: 0.572

Gnomad ASJ AF: 0.408

Gnomad EAS AF: 0.565

Gnomad SAS AF: 0.449

Gnomad FIN AF: 0.454

Gnomad MID AF: 0.369

Gnomad NFE AF: 0.407

Gnomad OTH AF: 0.446

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

GnomAD4 genome AF: 0.428 AC: 64966 AN: 151902 Hom.: 14422 Cov.: 32 AF XY: 0.434 AC XY: 32199 AN XY: 74232

African (AFR) AF: 0.383 AC: 15873 AN: 41422

American (AMR) AF: 0.573 AC: 8749 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.408 AC: 1413 AN: 3464

East Asian (EAS) AF: 0.565 AC: 2912 AN: 5152

South Asian (SAS) AF: 0.450 AC: 2162 AN: 4808

European-Finnish (FIN) AF: 0.454 AC: 4791 AN: 10552

Middle Eastern (MID) AF: 0.370 AC: 108 AN: 292

European-Non Finnish (NFE) AF: 0.407 AC: 27640 AN: 67926

Other (OTH) AF: 0.450 AC: 948 AN: 2108

Alfa AF: 0.418 Hom.: 21370

Bravo AF: 0.442

Asia WGS AF: 0.513 AC: 1779 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.1
DANN	Benign	0.39
PhyloP100		-0.25
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: rs10935317; hg19: chr3-139026525;