rs17211964

Positions:

• chr14-22835063-G-C

Variant summary

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

The variant allele was found at a frequency of 0.054 in 152,140 control chromosomes in the GnomAD database, including 305 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 0.054 (305 hom., cov: 32)
  • Exomes 𝑓: 0.063 (0 hom.)
• Consequence: intergenic_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.375

Genes affected

(HGNC:):

MRPL52 (HGNC:16655): (mitochondrial ribosomal protein L52) 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 39S subunit protein which has no bacterial homolog. Multiple transcript variants encoding different protein isoforms were identified through sequence analysis. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0675 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MRPL52	NM_180982.3	c.*742G>C		downstream_gene_variant		ENST00000397496.7	NP_851313.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MRPL52	ENST00000397496.7	c.*742G>C		downstream_gene_variant		2	NM_180982.3	ENSP00000380633.3
MRPL52	ENST00000355151.9	c.*742G>C		downstream_gene_variant		1		ENSP00000347277.5

Frequencies

GnomAD3 genomes AF: 0.0540 AC: 8206 AN: 151974 Hom.: 304 Cov.: 32

Gnomad AFR AF: 0.0110

Gnomad AMI AF: 0.140

Gnomad AMR AF: 0.0619

Gnomad ASJ AF: 0.120

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.0251

Gnomad FIN AF: 0.122

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.0692

Gnomad OTH AF: 0.0527

GnomAD4 exome AF: 0.0625 AC: 3 AN: 48 Hom.: 0 Cov.: 0 AF XY: 0.0667 AC XY: 2 AN XY: 30

Gnomad4 AFR exome AF: 0.00

Gnomad4 FIN exome AF: 0.0625

Gnomad4 NFE exome AF: 0.0714

GnomAD4 genome AF: 0.0540 AC: 8208 AN: 152092 Hom.: 305 Cov.: 32 AF XY: 0.0558 AC XY: 4150 AN XY: 74336

Gnomad4 AFR AF: 0.0110

Gnomad4 AMR AF: 0.0619

Gnomad4 ASJ AF: 0.120

Gnomad4 EAS AF: 0.00154

Gnomad4 SAS AF: 0.0253

Gnomad4 FIN AF: 0.122

Gnomad4 NFE AF: 0.0692

Gnomad4 OTH AF: 0.0526

Alfa AF: 0.0652 Hom.: 56

Bravo AF: 0.0477

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	14
DANN	Benign	0.77

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs17211964; hg19: chr14-23304272;