chr3-139324394-C-G

Position:

• chr3-139324394-C-G

Variant summary

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

The XM_047449421.1(LOC124909439):​c.130-7490G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.928 in 152,186 control chromosomes in the GnomAD database, including 65,754 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 0.93 (65754 hom., cov: 31)
• Consequence: LOC124909439 XM_047449421.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.834

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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.956 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC124909439	XM_047449421.1	c.130-7490G>C		intron_variant			XP_047305377.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
	ENST00000656212.1	n.302-7490G>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.928 AC: 141183 AN: 152068 Hom.: 65717 Cov.: 31

Gnomad AFR AF: 0.864

Gnomad AMI AF: 0.952

Gnomad AMR AF: 0.943

Gnomad ASJ AF: 0.925

Gnomad EAS AF: 0.978

Gnomad SAS AF: 0.955

Gnomad FIN AF: 0.974

Gnomad MID AF: 0.918

Gnomad NFE AF: 0.951

Gnomad OTH AF: 0.938

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

GnomAD4 genome AF: 0.928 AC: 141276 AN: 152186 Hom.: 65754 Cov.: 31 AF XY: 0.930 AC XY: 69238 AN XY: 74412

Gnomad4 AFR AF: 0.864

Gnomad4 AMR AF: 0.943

Gnomad4 ASJ AF: 0.925

Gnomad4 EAS AF: 0.978

Gnomad4 SAS AF: 0.956

Gnomad4 FIN AF: 0.974

Gnomad4 NFE AF: 0.951

Gnomad4 OTH AF: 0.936

Alfa AF: 0.942 Hom.: 7888

Bravo AF: 0.924

Asia WGS AF: 0.947 AC: 3294 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.50
DANN	Benign	0.33

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: rs4894410; hg19: chr3-139043236;