Genetic Variant MRPL3:c.894+27dupT (chr3-131468063-G-GA) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_007208.4(MRPL3):c.894+27dupT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000359 in 1,138,080 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00021 ( 0 hom., cov: 29)

Exomes 𝑓: 0.00038 ( 0 hom. )

Consequence

MRPL3
NM_007208.4 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.70

Publications

0 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: Labcorp Genetics (formerly Invitae), Ambry Genetics
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: Uncertain_significance. The variant received 0 ACMG points.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRPL3	NM_007208.4	MANE Select	c.894+27dupT		intron	N/A	NP_009139.1	P09001

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MRPL3	ENST00000264995.8	TSL:1 MANE Select	c.894+27_894+28insT	intron	N/A	ENSP00000264995.2	P09001
MRPL3	ENST00000425847.6	TSL:2	c.975+27_975+28insT	intron	N/A	ENSP00000398536.2	E7ETU7
MRPL3	ENST00000511168.5	TSL:2	c.936+27_936+28insT	intron	N/A	ENSP00000424107.1	H0Y9G6

Frequencies

GnomAD3 genomes

AF:

0.000213

AC:

AN:

145494

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00600

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000151

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000326

AC:

AN:

147252

AF XY:

0.000282

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000259

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00454

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000529

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000381

AC:

378

AN:

992514

Hom.:

Cov.:

AF XY:

0.000411

AC XY:

206

AN XY:

501802

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.000151

AC:

AN:

19892

American (AMR)

AF:

0.000335

AC:

AN:

20874

Ashkenazi Jewish (ASJ)

AF:

0.000167

AC:

AN:

18010

East Asian (EAS)

AF:

0.00127

AC:

AN:

31392

South Asian (SAS)

AF:

0.000411

AC:

AN:

51108

European-Finnish (FIN)

AF:

0.0000653

AC:

AN:

45958

Middle Eastern (MID)

AF:

0.000238

AC:

AN:

4200

European-Non Finnish (NFE)

AF:

0.000377

AC:

286

AN:

759238

Other (OTH)

AF:

0.000335

AC:

AN:

41842

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.246

Heterozygous variant carriers

113

169

226

282

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<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:

0.000213

AC:

AN:

145566

Hom.:

Cov.:

AF XY:

0.000254

AC XY:

AN XY:

70816

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

39296

American (AMR)

AF:

0.00

AC:

AN:

14574

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3412

East Asian (EAS)

AF:

0.00602

AC:

AN:

4986

South Asian (SAS)

AF:

0.00

AC:

AN:

4630

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9304

Middle Eastern (MID)

AF:

0.00

AC:

AN:

278

European-Non Finnish (NFE)

AF:

0.0000151

AC:

AN:

66188

Other (OTH)

AF:

0.00

AC:

AN:

2010

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

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:

0.00

Hom.:

Bravo

AF:

0.000200

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

-2.7

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

3-131468063-GAAA-GAAAA

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over