rs7640145

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr3-139015372-G-A
• chr3-139015372-G-T

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MRPS22	ENST00000495075.5	c.-143+9277G>A		intron_variant	Intron 1 of 9	1		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

Gnomad4 AFR AF: 0.705

Gnomad4 AMR AF: 0.849

Gnomad4 ASJ AF: 0.834

Gnomad4 EAS AF: 0.970

Gnomad4 SAS AF: 0.866

Gnomad4 FIN AF: 0.870

Gnomad4 NFE AF: 0.830

Gnomad4 OTH AF: 0.801

Alfa AF: 0.828 Hom.: 105316

Bravo AF: 0.802

Asia WGS AF: 0.902 AC: 3135 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	9.5
DANN	Benign	0.89

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: rs7640145; hg19: chr3-138734214;