3-139307597-G-C

Variant names:

• chr3-139307597-G-C
• rs10935316
• ENST00000495075.5:c.-71-36359G>C

Variant summary

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

The ENST00000495075.5(MRPS22):​c.-71-36359G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.727 in 152,042 control chromosomes in the GnomAD database, including 41,205 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 0.73 (41205 hom., cov: 32)
• Consequence: MRPS22 ENST00000495075.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0480

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=-0.87).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.829 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MRPS22	ENST00000495075.5	c.-71-36359G>C		intron_variant	Intron 2 of 9	1		ENSP00000418008.1
MRPS22	ENST00000688697.1	c.-72+24701G>C		intron_variant	Intron 2 of 9			ENSP00000510396.1
MRPS22	ENST00000687538.1	c.-39+24701G>C		intron_variant	Intron 2 of 8			ENSP00000508887.1

Frequencies

GnomAD3 genomes AF: 0.727 AC: 110491 AN: 151924 Hom.: 41187 Cov.: 32

Gnomad AFR AF: 0.553

Gnomad AMI AF: 0.822

Gnomad AMR AF: 0.841

Gnomad ASJ AF: 0.822

Gnomad EAS AF: 0.607

Gnomad SAS AF: 0.827

Gnomad FIN AF: 0.767

Gnomad MID AF: 0.845

Gnomad NFE AF: 0.795

Gnomad OTH AF: 0.779

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

GnomAD4 genome AF: 0.727 AC: 110543 AN: 152042 Hom.: 41205 Cov.: 32 AF XY: 0.729 AC XY: 54185 AN XY: 74350

Gnomad4 AFR AF: 0.553

Gnomad4 AMR AF: 0.841

Gnomad4 ASJ AF: 0.822

Gnomad4 EAS AF: 0.607

Gnomad4 SAS AF: 0.828

Gnomad4 FIN AF: 0.767

Gnomad4 NFE AF: 0.795

Gnomad4 OTH AF: 0.780

Alfa AF: 0.687 Hom.: 2172

Bravo AF: 0.727

Asia WGS AF: 0.698 AC: 2430 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.1
DANN	Benign	0.60

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: rs10935316; hg19: chr3-139026439;