rs4764600

chr12-6492814-C-Gchr12-6492814-C-T

Variant summary

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

The NM_016497.4(MRPL51):c.190+48G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.292 in 1,520,864 control chromosomes in the GnomAD database, including 68,492 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 0.35 (10343 hom., cov: 32)
  • Exomes 𝑓: 0.29 (58149 hom.)
• Consequence: MRPL51 NM_016497.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.74

Genes affected

MRPL51 (HGNC:14044): (mitochondrial ribosomal protein L51) 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. Pseudogenes corresponding to this gene are found on chromosomes 4p and 21q. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.51 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MRPL51	NM_016497.4	c.190+48G>C		intron_variant		ENST00000229238.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MRPL51	ENST00000229238.5	c.190+48G>C		intron_variant		1	NM_016497.4	P1

Frequencies

GnomAD3 genomes AF: 0.353 AC: 53641 AN: 151812 Hom.: 10330 Cov.: 32

Gnomad AFR AF: 0.516

Gnomad AMI AF: 0.275

Gnomad AMR AF: 0.360

Gnomad ASJ AF: 0.433

Gnomad EAS AF: 0.222

Gnomad SAS AF: 0.264

Gnomad FIN AF: 0.258

Gnomad MID AF: 0.416

Gnomad NFE AF: 0.280

Gnomad OTH AF: 0.374

GnomAD3 exomes AF: 0.316 AC: 78865 AN: 249690 Hom.: 13307 AF XY: 0.309 AC XY: 41759 AN XY: 135182

Gnomad AFR exome AF: 0.521

Gnomad AMR exome AF: 0.414

Gnomad ASJ exome AF: 0.423

Gnomad EAS exome AF: 0.227

Gnomad SAS exome AF: 0.264

Gnomad FIN exome AF: 0.256

Gnomad NFE exome AF: 0.287

Gnomad OTH exome AF: 0.324

GnomAD4 exome AF: 0.285 AC: 390712 AN: 1368934 Hom.: 58149 Cov.: 26 AF XY: 0.285 AC XY: 195375 AN XY: 685604

Gnomad4 AFR exome AF: 0.531

Gnomad4 AMR exome AF: 0.410

Gnomad4 ASJ exome AF: 0.429

Gnomad4 EAS exome AF: 0.215

Gnomad4 SAS exome AF: 0.264

Gnomad4 FIN exome AF: 0.261

Gnomad4 NFE exome AF: 0.273

Gnomad4 OTH exome AF: 0.309

GnomAD4 genome AF: 0.353 AC: 53696 AN: 151930 Hom.: 10343 Cov.: 32 AF XY: 0.351 AC XY: 26086 AN XY: 74258

Gnomad4 AFR AF: 0.515

Gnomad4 AMR AF: 0.361

Gnomad4 ASJ AF: 0.433

Gnomad4 EAS AF: 0.222

Gnomad4 SAS AF: 0.266

Gnomad4 FIN AF: 0.258

Gnomad4 NFE AF: 0.280

Gnomad4 OTH AF: 0.370

Alfa AF: 0.256 Hom.: 947

Bravo AF: 0.372

Asia WGS AF: 0.284 AC: 989 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	0.14
Dann	Benign	0.32

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs4764600; hg19: chr12-6601980; COSMIC: COSV57519623; COSMIC: COSV57519623;