rs584059

Positions:

• chr3-139112244-G-T

Variant summary

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

The ENST00000495075.5(MRPS22):​c.-142-68046G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.787 in 152,038 control chromosomes in the GnomAD database, including 49,040 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 0.79 (49040 hom., cov: 31)
• Consequence: MRPS22 ENST00000495075.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.162

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]

BPESC1 (HGNC:13228): (blepharophimosis, epicanthus inversus and ptosis candidate 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.913 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BPESC1	NR_026783.3	n.2331+2939G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MRPS22	ENST00000495075.5	c.-142-68046G>T		intron_variant		1		ENSP00000418008	P4
BPESC1	ENST00000418282.2	n.2331+2939G>T		intron_variant, non_coding_transcript_variant		1
MRPS22	ENST00000495225.1	n.172+1669G>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.787 AC: 119586 AN: 151920 Hom.: 49012 Cov.: 31

Gnomad AFR AF: 0.553

Gnomad AMI AF: 0.927

Gnomad AMR AF: 0.730

Gnomad ASJ AF: 0.919

Gnomad EAS AF: 0.674

Gnomad SAS AF: 0.865

Gnomad FIN AF: 0.892

Gnomad MID AF: 0.864

Gnomad NFE AF: 0.919

Gnomad OTH AF: 0.810

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

GnomAD4 genome AF: 0.787 AC: 119659 AN: 152038 Hom.: 49040 Cov.: 31 AF XY: 0.786 AC XY: 58391 AN XY: 74332

Gnomad4 AFR AF: 0.553

Gnomad4 AMR AF: 0.730

Gnomad4 ASJ AF: 0.919

Gnomad4 EAS AF: 0.674

Gnomad4 SAS AF: 0.867

Gnomad4 FIN AF: 0.892

Gnomad4 NFE AF: 0.919

Gnomad4 OTH AF: 0.811

Alfa AF: 0.890 Hom.: 56799

Bravo AF: 0.761

Asia WGS AF: 0.708 AC: 2466 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	8.9
DANN	Benign	0.89

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs584059; hg19: chr3-138831086;