rs3751488

chr14-22834885-G-A

Variant summary

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

The NM_180982.3(MRPL52):c.*564G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.192 in 152,214 control chromosomes in the GnomAD database, including 3,193 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 0.19 (3190 hom., cov: 32)
  • Exomes 𝑓: 0.17 (3 hom.)
• Consequence: MRPL52 NM_180982.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.708

Genes affected

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 (EAS) allele frequency at 95% confidence interval = 0.345 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MRPL52	NM_180982.3	c.*564G>A		3_prime_UTR_variant	5/5	ENST00000397496.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MRPL52	ENST00000397496.7	c.*564G>A		3_prime_UTR_variant	5/5	2	NM_180982.3	A1
MRPL52	ENST00000355151.9	c.*564G>A		3_prime_UTR_variant	5/5	1		P4
MRPL52	ENST00000311892.10	n.950G>A		non_coding_transcript_exon_variant	5/5	3

Frequencies

GnomAD3 genomes AF: 0.192 AC: 29142 AN: 151860 Hom.: 3186 Cov.: 32

Gnomad AFR AF: 0.104

Gnomad AMI AF: 0.249

Gnomad AMR AF: 0.157

Gnomad ASJ AF: 0.159

Gnomad EAS AF: 0.357

Gnomad SAS AF: 0.223

Gnomad FIN AF: 0.238

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.232

Gnomad OTH AF: 0.193

GnomAD4 exome AF: 0.174 AC: 41 AN: 236 Hom.: 3 Cov.: 0 AF XY: 0.192 AC XY: 25 AN XY: 130

Gnomad4 AFR exome AF: 0.167

Gnomad4 AMR exome AF: 0.222

Gnomad4 EAS exome AF: 0.500

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.250

Gnomad4 NFE exome AF: 0.167

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.192 AC: 29170 AN: 151978 Hom.: 3190 Cov.: 32 AF XY: 0.193 AC XY: 14328 AN XY: 74252

Gnomad4 AFR AF: 0.104

Gnomad4 AMR AF: 0.157

Gnomad4 ASJ AF: 0.159

Gnomad4 EAS AF: 0.359

Gnomad4 SAS AF: 0.224

Gnomad4 FIN AF: 0.238

Gnomad4 NFE AF: 0.232

Gnomad4 OTH AF: 0.199

Alfa AF: 0.222 Hom.: 5878

Bravo AF: 0.184

Asia WGS AF: 0.310 AC: 1079 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	2.5
Dann	Benign	0.77

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: rs3751488; hg19: chr14-23304094;