rs10512809

chr3-131502030-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_007208.4(MRPL3):c.93-315T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0164 in 844,294 control chromosomes in the GnomAD database, including 148 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 0.013 (17 hom., cov: 33)
  • Exomes 𝑓: 0.017 (131 hom.)
• Consequence: MRPL3 NM_007208.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00200

Genes affected

MRPL3 (HGNC:10379): (mitochondrial ribosomal protein L3) 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 that belongs to the L3P ribosomal protein family. A pseudogene corresponding to this gene is found on chromosome 13q. [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).
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.0125 (1905/152338) while in subpopulation EAS AF= 0.0351 (182/5180). AF 95% confidence interval is 0.031. There are 17 homozygotes in gnomad4. There are 946 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 17 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MRPL3	NM_007208.4	c.93-315T>C		intron_variant		ENST00000264995.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MRPL3	ENST00000264995.8	c.93-315T>C		intron_variant		1	NM_007208.4	P1

Frequencies

GnomAD3 genomes AF: 0.0125 AC: 1908 AN: 152220 Hom.: 17 Cov.: 33

Gnomad AFR AF: 0.00367

Gnomad AMI AF: 0.0340

Gnomad AMR AF: 0.0116

Gnomad ASJ AF: 0.0202

Gnomad EAS AF: 0.0356

Gnomad SAS AF: 0.0196

Gnomad FIN AF: 0.00790

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0158

Gnomad OTH AF: 0.0158

GnomAD4 exome AF: 0.0173 AC: 11983 AN: 691956 Hom.: 131 AF XY: 0.0177 AC XY: 6360 AN XY: 358460

Gnomad4 AFR exome AF: 0.00319

Gnomad4 AMR exome AF: 0.00997

Gnomad4 ASJ exome AF: 0.0178

Gnomad4 EAS exome AF: 0.0373

Gnomad4 SAS exome AF: 0.0205

Gnomad4 FIN exome AF: 0.00798

Gnomad4 NFE exome AF: 0.0169

Gnomad4 OTH exome AF: 0.0193

GnomAD4 genome AF: 0.0125 AC: 1905 AN: 152338 Hom.: 17 Cov.: 33 AF XY: 0.0127 AC XY: 946 AN XY: 74492

Gnomad4 AFR AF: 0.00366

Gnomad4 AMR AF: 0.0116

Gnomad4 ASJ AF: 0.0202

Gnomad4 EAS AF: 0.0351

Gnomad4 SAS AF: 0.0194

Gnomad4 FIN AF: 0.00790

Gnomad4 NFE AF: 0.0158

Gnomad4 OTH AF: 0.0161

Alfa AF: 0.0136 Hom.: 2

Bravo AF: 0.0122

Asia WGS AF: 0.0280 AC: 99 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	3.6
Dann	Benign	0.49

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs10512809; hg19: chr3-131220874;