3-139326219-T-G

Position:

• chr3-139326219-T-G

Variant summary

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

The ENST00000495075.5(MRPS22):​c.-71-17737T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.905 in 152,198 control chromosomes in the GnomAD database, including 62,947 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 0.91 (62947 hom., cov: 31)
• Consequence: MRPS22 ENST00000495075.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.130

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]

LOC124909439 (HGNC:):

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 = 0.954 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC124909439	XM_047449421.1	c.130-9315A>C		intron_variant			XP_047305377.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
	ENST00000656212.1	n.302-9315A>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.905 AC: 137694 AN: 152080 Hom.: 62909 Cov.: 31

Gnomad AFR AF: 0.774

Gnomad AMI AF: 0.951

Gnomad AMR AF: 0.940

Gnomad ASJ AF: 0.916

Gnomad EAS AF: 0.975

Gnomad SAS AF: 0.904

Gnomad FIN AF: 0.974

Gnomad MID AF: 0.934

Gnomad NFE AF: 0.960

Gnomad OTH AF: 0.917

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

GnomAD4 genome AF: 0.905 AC: 137785 AN: 152198 Hom.: 62947 Cov.: 31 AF XY: 0.907 AC XY: 67542 AN XY: 74430

Gnomad4 AFR AF: 0.774

Gnomad4 AMR AF: 0.940

Gnomad4 ASJ AF: 0.916

Gnomad4 EAS AF: 0.975

Gnomad4 SAS AF: 0.905

Gnomad4 FIN AF: 0.974

Gnomad4 NFE AF: 0.960

Gnomad4 OTH AF: 0.915

Alfa AF: 0.928 Hom.: 10145

Bravo AF: 0.898

Asia WGS AF: 0.916 AC: 3187 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.5
DANN	Benign	0.68

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: rs1873668; hg19: chr3-139045061;