rs1873666

chr3-139321819-A-Gchr3-139321819-A-T

Variant summary

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

The ENST00000495075.5(MRPS22):c.-71-22137A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.848 in 152,144 control chromosomes in the GnomAD database, including 54,991 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 0.85 (54991 hom., cov: 31)
• Consequence: MRPS22 ENST00000495075.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.988

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=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.949 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LOC124909439	XM_047449421.1	c.130-4915T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
	ENST00000656212.1	n.302-4915T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.848 AC: 128879 AN: 152026 Hom.: 54954 Cov.: 31

Gnomad AFR AF: 0.771

Gnomad AMI AF: 0.893

Gnomad AMR AF: 0.867

Gnomad ASJ AF: 0.842

Gnomad EAS AF: 0.971

Gnomad SAS AF: 0.799

Gnomad FIN AF: 0.916

Gnomad MID AF: 0.755

Gnomad NFE AF: 0.874

Gnomad OTH AF: 0.833

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

GnomAD4 genome AF: 0.848 AC: 128971 AN: 152144 Hom.: 54991 Cov.: 31 AF XY: 0.850 AC XY: 63230 AN XY: 74382

Gnomad4 AFR AF: 0.771

Gnomad4 AMR AF: 0.867

Gnomad4 ASJ AF: 0.842

Gnomad4 EAS AF: 0.971

Gnomad4 SAS AF: 0.800

Gnomad4 FIN AF: 0.916

Gnomad4 NFE AF: 0.874

Gnomad4 OTH AF: 0.830

Alfa AF: 0.865 Hom.: 20339

Bravo AF: 0.844

Asia WGS AF: 0.870 AC: 3026 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	0.42
Dann	Benign	0.34

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: rs1873666; hg19: chr3-139040661;