3-131462839-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -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. 16/22 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

Publications

6 publications found

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 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

MRPL3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 Benign/Likely_benign. ClinVar VariationId 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 rank	MANE	Protein	UniProt
MRPL3	NM_007208.4 link	c.931G>A	p.Gly311Ser	missense_variant	Exon 10 of 10	ENST00000264995.8	NP_009139.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
MRPL3	ENST00000264995.8 link	c.931G>A	p.Gly311Ser	missense_variant	Exon 10 of 10	1	NM_007208.4	ENSP00000264995.2
MRPL3	ENST00000425847.6 link	c.1012G>A	p.Gly338Ser	missense_variant	Exon 11 of 11	2		ENSP00000398536.2
MRPL3	ENST00000511168.5 link	c.973G>A	p.Gly325Ser	missense_variant	Exon 10 of 10	2		ENSP00000424107.1
MRPL3	ENST00000510043.1 link	n.355G>A		non_coding_transcript_exon_variant	Exon 4 of 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

GnomAD2 exomes

AF:

0.00368

AC:

920

AN:

249772

AF XY:

0.00416

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 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

African (AFR)

AF:

0.00102

AC:

AN:

33348

American (AMR)

AF:

0.00310

AC:

138

AN:

44548

Ashkenazi Jewish (ASJ)

AF:

0.00288

AC:

AN:

26004

East Asian (EAS)

AF:

0.0000253

AC:

AN:

39596

South Asian (SAS)

AF:

0.00400

AC:

344

AN:

85986

European-Finnish (FIN)

AF:

0.00131

AC:

AN:

53350

Middle Eastern (MID)

AF:

0.0113

AC:

AN:

5754

European-Non Finnish (NFE)

AF:

0.00355

AC:

3947

AN:

1110430

Other (OTH)

AF:

0.00365

AC:

220

AN:

60266

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

221

442

663

884

1105

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

118

236

354

472

590

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00312

AC:

475

AN:

152120

Hom.:

Cov.:

AF XY:

0.00313

AC XY:

233

AN XY:

74352

show subpopulations

African (AFR)

AF:

0.000819

AC:

AN:

41506

American (AMR)

AF:

0.00373

AC:

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.00288

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5170

South Asian (SAS)

AF:

0.00374

AC:

AN:

4814

European-Finnish (FIN)

AF:

0.000189

AC:

AN:

10578

Middle Eastern (MID)

AF:

0.0136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00497

AC:

338

AN:

68004

Other (OTH)

AF:

0.00569

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

102

127

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00424

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

Feb 23, 2016

Mayo Clinic Laboratories, Mayo Clinic

Significance:Uncertain significance

Review Status:no assertion criteria provided

Collection Method:clinical testing

Oct 13, 2016

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Aug 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

MRPL3: BP4, BS2

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Jul 11, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Jan 28, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

MRPL3-related disorder

Benign:1

Mar 13, 2024

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

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

(source)

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;.

PhyloP100

-0.24

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

Vest4

0.083

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

Mutation Taster

=99/1

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over