3-139302297-T-C

Position:

• chr3-139302297-T-C

Variant summary

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

The ENST00000495075.5(MRPS22):​c.-71-41659T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.698 in 152,024 control chromosomes in the GnomAD database, including 37,658 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 0.70 (37658 hom., cov: 32)
• Consequence: MRPS22 ENST00000495075.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.39

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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.738 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MRPS22	ENST00000495075.5	c.-71-41659T>C		intron_variant		1		P4
MRPS22	ENST00000684961.1	c.-43+19401T>C		intron_variant
MRPS22	ENST00000687538.1	c.-39+19401T>C		intron_variant

Frequencies

GnomAD3 genomes AF: 0.698 AC: 106066 AN: 151906 Hom.: 37626 Cov.: 32

Gnomad AFR AF: 0.744

Gnomad AMI AF: 0.841

Gnomad AMR AF: 0.514

Gnomad ASJ AF: 0.773

Gnomad EAS AF: 0.560

Gnomad SAS AF: 0.617

Gnomad FIN AF: 0.702

Gnomad MID AF: 0.729

Gnomad NFE AF: 0.722

Gnomad OTH AF: 0.680

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

GnomAD4 genome AF: 0.698 AC: 106141 AN: 152024 Hom.: 37658 Cov.: 32 AF XY: 0.693 AC XY: 51490 AN XY: 74328

Gnomad4 AFR AF: 0.745

Gnomad4 AMR AF: 0.513

Gnomad4 ASJ AF: 0.773

Gnomad4 EAS AF: 0.559

Gnomad4 SAS AF: 0.616

Gnomad4 FIN AF: 0.702

Gnomad4 NFE AF: 0.722

Gnomad4 OTH AF: 0.676

Alfa AF: 0.708 Hom.: 53604

Bravo AF: 0.682

Asia WGS AF: 0.583 AC: 2032 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.30
DANN	Benign	0.43

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: rs4894405; hg19: chr3-139021139;