chr3-139122751-T-C

Position:

• chr3-139122751-T-C

Variant summary

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

The ENST00000495075.5(MRPS22):​c.-142-57539T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.706 in 152,026 control chromosomes in the GnomAD database, including 40,310 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 0.71 (40310 hom., cov: 31)
• Consequence: MRPS22 ENST00000495075.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.08

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.941 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BPESC1	NR_026783.3	n.2332-1230T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MRPS22	ENST00000495075.5	c.-142-57539T>C		intron_variant		1		ENSP00000418008.1
BPESC1	ENST00000418282.2	n.2332-1230T>C		intron_variant		1
MRPS22	ENST00000495225.1	n.172+12176T>C		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.707 AC: 107330 AN: 151908 Hom.: 40301 Cov.: 31

Gnomad AFR AF: 0.433

Gnomad AMI AF: 0.861

Gnomad AMR AF: 0.776

Gnomad ASJ AF: 0.821

Gnomad EAS AF: 0.963

Gnomad SAS AF: 0.843

Gnomad FIN AF: 0.854

Gnomad MID AF: 0.772

Gnomad NFE AF: 0.796

Gnomad OTH AF: 0.724

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

GnomAD4 genome AF: 0.706 AC: 107380 AN: 152026 Hom.: 40310 Cov.: 31 AF XY: 0.715 AC XY: 53183 AN XY: 74342

Gnomad4 AFR AF: 0.433

Gnomad4 AMR AF: 0.776

Gnomad4 ASJ AF: 0.821

Gnomad4 EAS AF: 0.963

Gnomad4 SAS AF: 0.844

Gnomad4 FIN AF: 0.854

Gnomad4 NFE AF: 0.796

Gnomad4 OTH AF: 0.722

Alfa AF: 0.778 Hom.: 21322

Bravo AF: 0.689

Asia WGS AF: 0.856 AC: 2971 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.4
DANN	Benign	0.72

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: rs940187; hg19: chr3-138841593;