chr3-131502030-A-G

Variant names:

• chr3-131502030-A-G
• rs10512809
• NM_007208.4:c.93-315T>C

Variant summary

Our verdict is Benign. The variant received -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
• 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: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• 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=-0.8).
• 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 the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 17 AR gene

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRPL3	NM_007208.4	MANE Select	c.93-315T>C		intron	N/A	NP_009139.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRPL3	ENST00000264995.8	TSL:1 MANE Select	c.93-315T>C		intron	N/A	ENSP00000264995.2
	MRPL3	ENST00000425847.6	TSL:2	c.93-106T>C		intron	N/A	ENSP00000398536.2
	MRPL3	ENST00000511168.5	TSL:2	c.135-315T>C		intron	N/A	ENSP00000424107.1

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

African (AFR) AF: 0.00319 AC: 53 AN: 16620

American (AMR) AF: 0.00997 AC: 207 AN: 20768

Ashkenazi Jewish (ASJ) AF: 0.0178 AC: 298 AN: 16732

East Asian (EAS) AF: 0.0373 AC: 1189 AN: 31904

South Asian (SAS) AF: 0.0205 AC: 1099 AN: 53644

European-Finnish (FIN) AF: 0.00798 AC: 243 AN: 30466

Middle Eastern (MID) AF: 0.0115 AC: 29 AN: 2532

European-Non Finnish (NFE) AF: 0.0169 AC: 8208 AN: 485258

Other (OTH) AF: 0.0193 AC: 657 AN: 34032

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

African (AFR) AF: 0.00366 AC: 152 AN: 41576

American (AMR) AF: 0.0116 AC: 177 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0202 AC: 70 AN: 3466

East Asian (EAS) AF: 0.0351 AC: 182 AN: 5180

South Asian (SAS) AF: 0.0194 AC: 94 AN: 4834

European-Finnish (FIN) AF: 0.00790 AC: 84 AN: 10628

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.0158 AC: 1073 AN: 68032

Other (OTH) AF: 0.0161 AC: 34 AN: 2114

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	3.6
DANN	Benign	0.49
PhyloP100		-0.0020
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs10512809; hg19: chr3-131220874; COSMIC: COSV107300488; COSMIC: COSV107300488;