rs4243399

chr3-139332068-G-Achr3-139332068-G-C

Variant summary

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

The ENST00000495075.5(MRPS22):c.-71-11888G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.888 in 152,246 control chromosomes in the GnomAD database, including 60,900 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 0.89 (60900 hom., cov: 32)
• Consequence: MRPS22 ENST00000495075.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.384

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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.951 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LOC124909439	XM_047449421.1	c.129+8502C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
	ENST00000656212.1	n.301+8502C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.888 AC: 135113 AN: 152128 Hom.: 60869 Cov.: 32

Gnomad AFR AF: 0.724

Gnomad AMI AF: 0.951

Gnomad AMR AF: 0.928

Gnomad ASJ AF: 0.896

Gnomad EAS AF: 0.972

Gnomad SAS AF: 0.894

Gnomad FIN AF: 0.974

Gnomad MID AF: 0.914

Gnomad NFE AF: 0.957

Gnomad OTH AF: 0.902

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

GnomAD4 genome AF: 0.888 AC: 135192 AN: 152246 Hom.: 60900 Cov.: 32 AF XY: 0.891 AC XY: 66319 AN XY: 74450

Gnomad4 AFR AF: 0.723

Gnomad4 AMR AF: 0.929

Gnomad4 ASJ AF: 0.896

Gnomad4 EAS AF: 0.972

Gnomad4 SAS AF: 0.895

Gnomad4 FIN AF: 0.974

Gnomad4 NFE AF: 0.957

Gnomad4 OTH AF: 0.900

Alfa AF: 0.909 Hom.: 10370

Bravo AF: 0.879

Asia WGS AF: 0.908 AC: 3158 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
Cadd	Benign	2.5
Dann	Benign	0.56

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: rs4243399; hg19: chr3-139050910;