3-131462839-C-T

Position:

chr3-131462839-C-T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_007208.4(MRPL3):c.931G>A(p.Gly311Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00333 in 1,611,402 control chromosomes in the GnomAD database, including 23 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0031 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0034 ( 20 hom. )

Consequence

MRPL3
NM_007208.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts U:1B:6

Conservation

PhyloP100: -0.237

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 -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0067156255).

BP6

Variant 3-131462839-C-T is Benign according to our data. Variant chr3-131462839-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 374558.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MRPL3	NM_007208.4 linkuse as main transcript	c.931G>A	p.Gly311Ser	missense_variant	10/10	ENST00000264995.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
MRPL3	ENST00000264995.8 linkuse as main transcript	c.931G>A	p.Gly311Ser	missense_variant	10/10	1	NM_007208.4	P1
MRPL3	ENST00000425847.6 linkuse as main transcript	c.1012G>A	p.Gly338Ser	missense_variant	11/11	2
MRPL3	ENST00000511168.5 linkuse as main transcript	c.976G>A	p.Gly326Ser	missense_variant	10/10	2
MRPL3	ENST00000510043.1 linkuse as main transcript	n.355G>A		non_coding_transcript_exon_variant	4/4	2

Frequencies

GnomAD3 genomes

AF:

0.00314

AC:

477

AN:

152002

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000822

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00374

Gnomad ASJ

AF:

0.00288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00394

Gnomad FIN

AF:

0.000189

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.00497

Gnomad OTH

AF:

0.00575

GnomAD3 exomes

AF:

0.00368

AC:

920

AN:

249772

Hom.:

AF XY:

0.00416

AC XY:

561

AN XY:

134998

show subpopulations

Gnomad AFR exome

AF:

0.00105

Gnomad AMR exome

AF:

0.00292

Gnomad ASJ exome

AF:

0.00278

Gnomad EAS exome

AF:

0.0000546

Gnomad SAS exome

AF:

0.00364

Gnomad FIN exome

AF:

0.00139

Gnomad NFE exome

AF:

0.00519

Gnomad OTH exome

AF:

0.00773

GnomAD4 exome

AF:

0.00335

AC:

4894

AN:

1459282

Hom.:

Cov.:

AF XY:

0.00354

AC XY:

2571

AN XY:

725978

show subpopulations

Gnomad4 AFR exome

AF:

0.00102

Gnomad4 AMR exome

AF:

0.00310

Gnomad4 ASJ exome

AF:

0.00288

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.00400

Gnomad4 FIN exome

AF:

0.00131

Gnomad4 NFE exome

AF:

0.00355

Gnomad4 OTH exome

AF:

0.00365

GnomAD4 genome

AF:

0.00312

AC:

475

AN:

152120

Hom.:

Cov.:

AF XY:

0.00313

AC XY:

233

AN XY:

74352

show subpopulations

Gnomad4 AFR

AF:

0.000819

Gnomad4 AMR

AF:

0.00373

Gnomad4 ASJ

AF:

0.00288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00374

Gnomad4 FIN

AF:

0.000189

Gnomad4 NFE

AF:

0.00497

Gnomad4 OTH

AF:

0.00569

Alfa

AF:

0.00406

Hom.:

Bravo

AF:

0.00327

TwinsUK

AF:

0.00189

AC:

ALSPAC

AF:

0.00234

AC:

ESP6500AA

AF:

0.00136

AC:

ESP6500EA

AF:

0.00465

AC:

ExAC

AF:

0.00376

AC:

456

Asia WGS

AF:

0.00231

AC:

AN:

3476

ClinVar

Significance: Benign/Likely benign

Submissions summary: Uncertain:1Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Uncertain:1Benign:5

Likely benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Oct 13, 2016	- -
Uncertain significance, no assertion criteria provided	clinical testing	Mayo Clinic Laboratories, Mayo Clinic	Feb 23, 2016	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Aug 01, 2024	MRPL3: BP4, BS2 -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 11, 2019	- -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 24, 2024	- -

MRPL3-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 13, 2024

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.60

CADD

Benign

4.5

DANN

Benign

0.55

DEOGEN2

Benign

0.014

T;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.027

LIST_S2

Benign

0.29

T;T

M_CAP

Benign

0.0031

MetaRNN

Benign

0.0067

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

-1.1

N;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.32

PROVEAN

Benign

1.5

N;N

REVEL

Benign

0.017

Sift

Benign

0.79

T;T

Sift4G

Benign

0.73

T;T

Polyphen

0.0

B;B

Vest4

0.083

MVP

0.65

MPC

0.066

ClinPred

0.0020

GERP RS

-4.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.065

gMVP

0.22

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