chr3-139015372-G-A

Position:

• chr3-139015372-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000495075.5(MRPS22):​c.-143+9277G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.807 in 152,140 control chromosomes in the GnomAD database, including 49,958 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 0.81 (49958 hom., cov: 32)
• Consequence: MRPS22 ENST00000495075.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.796

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.948 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.-143+9277G>A		intron_variant		1		ENSP00000418008	P4

Frequencies

GnomAD3 genomes AF: 0.807 AC: 122672 AN: 152022 Hom.: 49945 Cov.: 32

Gnomad AFR AF: 0.705

Gnomad AMI AF: 0.863

Gnomad AMR AF: 0.849

Gnomad ASJ AF: 0.834

Gnomad EAS AF: 0.971

Gnomad SAS AF: 0.866

Gnomad FIN AF: 0.870

Gnomad MID AF: 0.848

Gnomad NFE AF: 0.830

Gnomad OTH AF: 0.807

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

GnomAD4 genome AF: 0.807 AC: 122723 AN: 152140 Hom.: 49958 Cov.: 32 AF XY: 0.812 AC XY: 60384 AN XY: 74372

Gnomad4 AFR AF: 0.705

Gnomad4 AMR AF: 0.849

Gnomad4 ASJ AF: 0.834

Gnomad4 EAS AF: 0.970

Gnomad4 SAS AF: 0.866

Gnomad4 FIN AF: 0.870

Gnomad4 NFE AF: 0.830

Gnomad4 OTH AF: 0.801

Alfa AF: 0.828 Hom.: 105316

Bravo AF: 0.802

Asia WGS AF: 0.902 AC: 3135 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	9.5
DANN	Benign	0.89

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: rs7640145; hg19: chr3-138734214;