chr3-139287822-C-G

Position:

• chr3-139287822-C-G

Variant summary

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

The ENST00000495075.5(MRPS22):​c.-71-56134C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.211 in 152,178 control chromosomes in the GnomAD database, including 4,689 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 0.21 (4689 hom., cov: 33)
• Consequence: MRPS22 ENST00000495075.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0390

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]

LOC124906290 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.431 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC124906290	XR_007096115.1	n.5525C>G		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MRPS22	ENST00000495075.5	c.-71-56134C>G		intron_variant		1		ENSP00000418008	P4
MRPS22	ENST00000684961.1	c.-43+4926C>G		intron_variant				ENSP00000508439
MRPS22	ENST00000687538.1	c.-39+4926C>G		intron_variant				ENSP00000508887

Frequencies

GnomAD3 genomes AF: 0.211 AC: 32023 AN: 152060 Hom.: 4666 Cov.: 33

Gnomad AFR AF: 0.0653

Gnomad AMI AF: 0.0910

Gnomad AMR AF: 0.438

Gnomad ASJ AF: 0.246

Gnomad EAS AF: 0.443

Gnomad SAS AF: 0.385

Gnomad FIN AF: 0.200

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.218

Gnomad OTH AF: 0.246

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

GnomAD4 genome AF: 0.211 AC: 32058 AN: 152178 Hom.: 4689 Cov.: 33 AF XY: 0.218 AC XY: 16252 AN XY: 74388

Gnomad4 AFR AF: 0.0651

Gnomad4 AMR AF: 0.439

Gnomad4 ASJ AF: 0.246

Gnomad4 EAS AF: 0.443

Gnomad4 SAS AF: 0.386

Gnomad4 FIN AF: 0.200

Gnomad4 NFE AF: 0.218

Gnomad4 OTH AF: 0.252

Alfa AF: 0.197 Hom.: 477

Bravo AF: 0.224

Asia WGS AF: 0.424 AC: 1474 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	9.3
DANN	Benign	0.75

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: rs6802174; hg19: chr3-139006664;