chr3-131494662-C-T

Variant names:

• chr3-131494662-C-T
• rs2035573
• NM_007208.4:c.468+3517G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_007208.4(MRPL3):​c.468+3517G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.739 in 152,036 control chromosomes in the GnomAD database, including 42,799 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 0.74 (42799 hom., cov: 32)
• Consequence: MRPL3 NM_007208.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.75
• Publications: 1 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.896 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRPL3	NM_007208.4	MANE Select	c.468+3517G>A		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.468+3517G>A		intron	N/A	ENSP00000264995.2
	MRPL3	ENST00000425847.6	TSL:2	c.549+3517G>A		intron	N/A	ENSP00000398536.2
	MRPL3	ENST00000511168.5	TSL:2	c.510+3517G>A		intron	N/A	ENSP00000424107.1

Frequencies

GnomAD3 genomes AF: 0.739 AC: 112298 AN: 151918 Hom.: 42742 Cov.: 32

Gnomad AFR AF: 0.904

Gnomad AMI AF: 0.729

Gnomad AMR AF: 0.614

Gnomad ASJ AF: 0.783

Gnomad EAS AF: 0.365

Gnomad SAS AF: 0.617

Gnomad FIN AF: 0.668

Gnomad MID AF: 0.813

Gnomad NFE AF: 0.713

Gnomad OTH AF: 0.741

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

GnomAD4 genome AF: 0.739 AC: 112405 AN: 152036 Hom.: 42799 Cov.: 32 AF XY: 0.731 AC XY: 54331 AN XY: 74292

African (AFR) AF: 0.904 AC: 37522 AN: 41516

American (AMR) AF: 0.614 AC: 9364 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.783 AC: 2714 AN: 3468

East Asian (EAS) AF: 0.365 AC: 1889 AN: 5172

South Asian (SAS) AF: 0.618 AC: 2977 AN: 4816

European-Finnish (FIN) AF: 0.668 AC: 7025 AN: 10522

Middle Eastern (MID) AF: 0.806 AC: 237 AN: 294

European-Non Finnish (NFE) AF: 0.713 AC: 48448 AN: 67974

Other (OTH) AF: 0.743 AC: 1566 AN: 2108

Alfa AF: 0.755 Hom.: 6522

Bravo AF: 0.738

Asia WGS AF: 0.542 AC: 1874 AN: 3454

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	6.3
DANN	Benign	0.61
PhyloP100		1.7
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: rs2035573; hg19: chr3-131213506;