rs10512807

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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]

MRPL3 Gene-Disease associations (from GenCC):

• combined oxidative phosphorylation defect type 9

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• mitochondrial disease

  Inheritance: AR Classification: MODERATE Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007208.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRPL3	NM_007208.4	MANE Select	c.469-3490T>C		intron	N/A	NP_009139.1	P09001

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRPL3	ENST00000264995.8	TSL:1 MANE Select	c.469-3490T>C		intron	N/A	ENSP00000264995.2	P09001
	MRPL3	ENST00000425847.6	TSL:2	c.550-3490T>C		intron	N/A	ENSP00000398536.2	E7ETU7
	MRPL3	ENST00000511168.5	TSL:2	c.511-3490T>C		intron	N/A	ENSP00000424107.1	H0Y9G6

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

African (AFR) AF: 0.214 AC: 8871 AN: 41516

American (AMR) AF: 0.0390 AC: 596 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0202 AC: 70 AN: 3470

East Asian (EAS) AF: 0.0356 AC: 184 AN: 5172

South Asian (SAS) AF: 0.0207 AC: 100 AN: 4820

European-Finnish (FIN) AF: 0.00809 AC: 86 AN: 10628

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0164 AC: 1116 AN: 68028

Other (OTH) AF: 0.0662 AC: 140 AN: 2114

Alfa AF: 0.0342 Hom.: 1177

Bravo AF: 0.0812

Asia WGS AF: 0.0410 AC: 143 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.1
DANN	Benign	0.34
PhyloP100		0.055
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10512807; hg19: chr3-131212414;