rs2291382

Variant names:

Variant summary

Our verdict is Benign. The variant received -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

Publications

8 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 -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 VariationId is 380042.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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 rank	MANE	Protein	UniProt
MRPL3	NM_007208.4 link	c.816+12A>C		intron_variant	Intron 8 of 9	ENST00000264995.8	NP_009139.1	P09001

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MRPL3	ENST00000264995.8 link	c.816+12A>C		intron_variant	Intron 8 of 9	1	NM_007208.4	ENSP00000264995.2		P09001

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

GnomAD2 exomes

AF:

0.146

AC:

35414

AN:

242578

AF XY:

0.155

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 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

African (AFR)

AF:

0.0262

AC:

860

AN:

32766

American (AMR)

AF:

0.0582

AC:

2514

AN:

43222

Ashkenazi Jewish (ASJ)

AF:

0.258

AC:

6623

AN:

25648

East Asian (EAS)

AF:

0.0692

AC:

2729

AN:

39464

South Asian (SAS)

AF:

0.229

AC:

19276

AN:

84156

European-Finnish (FIN)

AF:

0.174

AC:

9231

AN:

53130

Middle Eastern (MID)

AF:

0.158

AC:

902

AN:

5698

European-Non Finnish (NFE)

AF:

0.161

AC:

176486

AN:

1095458

Other (OTH)

AF:

0.150

AC:

8937

AN:

59508

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

7612

15224

22835

30447

38059

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6164

12328

18492

24656

30820

<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:

0.120

AC:

18243

AN:

152174

Hom.:

1459

Cov.:

AF XY:

0.121

AC XY:

9022

AN XY:

74410

show subpopulations

African (AFR)

AF:

0.0318

AC:

1322

AN:

41548

American (AMR)

AF:

0.0814

AC:

1244

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.259

AC:

899

AN:

3466

East Asian (EAS)

AF:

0.0632

AC:

328

AN:

5186

South Asian (SAS)

AF:

0.229

AC:

1102

AN:

4816

European-Finnish (FIN)

AF:

0.163

AC:

1723

AN:

10596

Middle Eastern (MID)

AF:

0.207

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.164

AC:

11152

AN:

67956

Other (OTH)

AF:

0.127

AC:

268

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

786

1573

2359

3146

3932

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

222

444

666

888

1110

<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:

0.151

Hom.:

6102

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

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

Dec 18, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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

(source)

DANN

Benign

0.61

PhyloP100

-0.034

Mutation Taster

=100/0

polymorphism (auto)

(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