ENST00000495075.5:c.-143+9277G>A

Variant names:

• chr3-139015372-G-A
• rs7640145
• ENST00000495075.5:c.-143+9277G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000495075.5(MRPS22):​c.-143+9277G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.807 in 152,140 control chromosomes in the GnomAD database, including 49,958 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 0.81 (49958 hom., cov: 32)
• Consequence: MRPS22 ENST00000495075.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.796
• Publications: 5 publications found

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]

MRPS22 Gene-Disease associations (from GenCC):

• mitochondrial disease

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• hypotonia with lactic acidemia and hyperammonemia

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, G2P
• 46 XX gonadal dysgenesis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• ovarian dysgenesis 7

  Inheritance: AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.948 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000495075.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRPS22	ENST00000495075.5	TSL:1	c.-143+9277G>A		intron	N/A	ENSP00000418008.1

Frequencies

GnomAD3 genomes AF: 0.807 AC: 122672 AN: 152022 Hom.: 49945 Cov.: 32

Gnomad AFR AF: 0.705

Gnomad AMI AF: 0.863

Gnomad AMR AF: 0.849

Gnomad ASJ AF: 0.834

Gnomad EAS AF: 0.971

Gnomad SAS AF: 0.866

Gnomad FIN AF: 0.870

Gnomad MID AF: 0.848

Gnomad NFE AF: 0.830

Gnomad OTH AF: 0.807

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

GnomAD4 genome AF: 0.807 AC: 122723 AN: 152140 Hom.: 49958 Cov.: 32 AF XY: 0.812 AC XY: 60384 AN XY: 74372

African (AFR) AF: 0.705 AC: 29222 AN: 41452

American (AMR) AF: 0.849 AC: 12991 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.834 AC: 2891 AN: 3468

East Asian (EAS) AF: 0.970 AC: 5031 AN: 5184

South Asian (SAS) AF: 0.866 AC: 4170 AN: 4814

European-Finnish (FIN) AF: 0.870 AC: 9214 AN: 10586

Middle Eastern (MID) AF: 0.850 AC: 250 AN: 294

European-Non Finnish (NFE) AF: 0.830 AC: 56478 AN: 68022

Other (OTH) AF: 0.801 AC: 1691 AN: 2112

Alfa AF: 0.824 Hom.: 220720

Bravo AF: 0.802

Asia WGS AF: 0.902 AC: 3135 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	9.5
DANN	Benign	0.89
PhyloP100		0.80
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7640145; hg19: chr3-138734214;