3-139176109-C-T

Position:

• chr3-139176109-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000495075.5(MRPS22):​c.-142-4181C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.364 in 152,006 control chromosomes in the GnomAD database, including 10,247 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 0.36 (10247 hom., cov: 33)
• Consequence: MRPS22 ENST00000495075.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.929

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]

ACMG classification

Verdict is Benign. Variant got -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 = 0.388 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MRPS22	ENST00000495075.5	c.-142-4181C>T		intron_variant		1		ENSP00000418008	P4
MRPS22	ENST00000495225.1	n.459+12899C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.364 AC: 55224 AN: 151888 Hom.: 10238 Cov.: 33

Gnomad AFR AF: 0.352

Gnomad AMI AF: 0.481

Gnomad AMR AF: 0.288

Gnomad ASJ AF: 0.376

Gnomad EAS AF: 0.402

Gnomad SAS AF: 0.314

Gnomad FIN AF: 0.330

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.392

Gnomad OTH AF: 0.348

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

GnomAD4 genome AF: 0.364 AC: 55260 AN: 152006 Hom.: 10247 Cov.: 33 AF XY: 0.357 AC XY: 26510 AN XY: 74306

Gnomad4 AFR AF: 0.352

Gnomad4 AMR AF: 0.287

Gnomad4 ASJ AF: 0.376

Gnomad4 EAS AF: 0.402

Gnomad4 SAS AF: 0.313

Gnomad4 FIN AF: 0.330

Gnomad4 NFE AF: 0.392

Gnomad4 OTH AF: 0.348

Alfa AF: 0.372 Hom.: 1318

Bravo AF: 0.358

Asia WGS AF: 0.309 AC: 1077 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.0
DANN	Benign	0.63

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

Publications

LitVar

Other links and lift over

dbSNP: rs10935309; hg19: chr3-138894951;