Variant rs2291382 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_007208.4(MRPL3):c.816+12A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.154 in 1,591,224 control chromosomes in the GnomAD database, including 21,091 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.12 ( 1459 hom., cov: 32)

Exomes 𝑓: 0.16 ( 19632 hom. )

Consequence

MRPL3
NM_007208.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.0340

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 3-131469684-T-G is Benign according to our data. Variant chr3-131469684-T-G is described in ClinVar as [Benign]. Clinvar id is 380042.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-131469684-T-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.218 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MRPL3	NM_007208.4 linkuse as main transcript	c.816+12A>C		intron_variant		ENST00000264995.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MRPL3	ENST00000264995.8 linkuse as main transcript	c.816+12A>C		intron_variant		1	NM_007208.4	P1

Frequencies

GnomAD3 genomes

AF:

0.120

AC:

18238

AN:

152056

Hom.:

1457

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0319

Gnomad AMI

AF:

0.158

Gnomad AMR

AF:

0.0814

Gnomad ASJ

AF:

0.259

Gnomad EAS

AF:

0.0631

Gnomad SAS

AF:

0.229

Gnomad FIN

AF:

0.163

Gnomad MID

AF:

0.199

Gnomad NFE

AF:

0.164

Gnomad OTH

AF:

0.123

GnomAD3 exomes

AF:

0.146

AC:

35414

AN:

242578

Hom.:

3189

AF XY:

0.155

AC XY:

20359

AN XY:

131056

show subpopulations

Gnomad AFR exome

AF:

0.0287

Gnomad AMR exome

AF:

0.0545

Gnomad ASJ exome

AF:

0.266

Gnomad EAS exome

AF:

0.0558

Gnomad SAS exome

AF:

0.230

Gnomad FIN exome

AF:

0.172

Gnomad NFE exome

AF:

0.167

Gnomad OTH exome

AF:

0.145

GnomAD4 exome

AF:

0.158

AC:

227558

AN:

1439050

Hom.:

19632

Cov.:

AF XY:

0.162

AC XY:

115751

AN XY:

716578

show subpopulations

Gnomad4 AFR exome

AF:

0.0262

Gnomad4 AMR exome

AF:

0.0582

Gnomad4 ASJ exome

AF:

0.258

Gnomad4 EAS exome

AF:

0.0692

Gnomad4 SAS exome

AF:

0.229

Gnomad4 FIN exome

AF:

0.174

Gnomad4 NFE exome

AF:

0.161

Gnomad4 OTH exome

AF:

0.150

GnomAD4 genome

AF:

0.120

AC:

18243

AN:

152174

Hom.:

1459

Cov.:

AF XY:

0.121

AC XY:

9022

AN XY:

74410

show subpopulations

Gnomad4 AFR

AF:

0.0318

Gnomad4 AMR

AF:

0.0814

Gnomad4 ASJ

AF:

0.259

Gnomad4 EAS

AF:

0.0632

Gnomad4 SAS

AF:

0.229

Gnomad4 FIN

AF:

0.163

Gnomad4 NFE

AF:

0.164

Gnomad4 OTH

AF:

0.127

Alfa

AF:

0.160

Hom.:

4371

Bravo

AF:

0.106

Asia WGS

AF:

0.159

AC:

553

AN:

3474

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 30, 2024	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Dec 18, 2015

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

4.1

DANN

Benign

0.61

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over