rs10512807

Variant names:

• chr3-131493570-A-G
• rs10512807
• NM_007208.4:c.469-3490T>C

Variant summary

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

The NM_007208.4(MRPL3):​c.469-3490T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0736 in 152,254 control chromosomes in the GnomAD database, including 1,049 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 0.074 (1049 hom., cov: 32)
• Consequence: MRPL3 NM_007208.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0550

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.21 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MRPL3	NM_007208.4	c.469-3490T>C		intron_variant	Intron 4 of 9	ENST00000264995.8	NP_009139.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MRPL3	ENST00000264995.8	c.469-3490T>C		intron_variant	Intron 4 of 9	1	NM_007208.4	ENSP00000264995.2

Frequencies

GnomAD3 genomes AF: 0.0734 AC: 11171 AN: 152136 Hom.: 1039 Cov.: 32

Gnomad AFR AF: 0.213

Gnomad AMI AF: 0.0340

Gnomad AMR AF: 0.0390

Gnomad ASJ AF: 0.0202

Gnomad EAS AF: 0.0361

Gnomad SAS AF: 0.0214

Gnomad FIN AF: 0.00809

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0164

Gnomad OTH AF: 0.0664

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0736 AC: 11204 AN: 152254 Hom.: 1049 Cov.: 32 AF XY: 0.0719 AC XY: 5353 AN XY: 74440

Gnomad4 AFR AF: 0.214

Gnomad4 AMR AF: 0.0390

Gnomad4 ASJ AF: 0.0202

Gnomad4 EAS AF: 0.0356

Gnomad4 SAS AF: 0.0207

Gnomad4 FIN AF: 0.00809

Gnomad4 NFE AF: 0.0164

Gnomad4 OTH AF: 0.0662

Alfa AF: 0.0257 Hom.: 271

Bravo AF: 0.0812

Asia WGS AF: 0.0410 AC: 143 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.1
DANN	Benign	0.34

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: rs10512807; hg19: chr3-131212414;