Genetic Variant MRPL43:p.Val156Val (chr10-100986746-C-T) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_032112.3(MRPL43):c.468G>A(p.Val156Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.232 in 1,613,614 control chromosomes in the GnomAD database, including 48,572 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.27 ( 6065 hom., cov: 32)

Exomes 𝑓: 0.23 ( 42507 hom. )

Consequence

MRPL43
NM_032112.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.118

Publications

58 publications found

Variant links:

Genes affected

MRPL43 (HGNC:14517): (mitochondrial ribosomal protein L43) 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. This gene and the gene for a semaphorin class 4 protein (SEMA4G) overlap at map location 10q24.31 and are transcribed in opposite directions. Sequence analysis identified multiple transcript variants encoding at least four different protein isoforms. [provided by RefSeq, Jul 2008]

MRPL43 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP7

Synonymous conserved (PhyloP=0.118 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.527 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MRPL43	NM_032112.3 link	c.468G>A	p.Val156Val	synonymous_variant	Exon 3 of 3	ENST00000318364.13	NP_115488.2	Q8N983-4A8K4V4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MRPL43	ENST00000318364.13 link	c.468G>A	p.Val156Val	synonymous_variant	Exon 3 of 3	1	NM_032112.3	ENSP00000315948.8		Q8N983-4

Frequencies

GnomAD3 genomes

AF:

0.265

AC:

40293

AN:

151904

Hom.:

6055

Cov.:

show subpopulations

Gnomad AFR

AF:

0.360

Gnomad AMI

AF:

0.153

Gnomad AMR

AF:

0.296

Gnomad ASJ

AF:

0.139

Gnomad EAS

AF:

0.544

Gnomad SAS

AF:

0.306

Gnomad FIN

AF:

0.172

Gnomad MID

AF:

0.180

Gnomad NFE

AF:

0.200

Gnomad OTH

AF:

0.248

GnomAD2 exomes

AF:

0.268

AC:

67393

AN:

251048

AF XY:

0.262

show subpopulations

Gnomad AFR exome

AF:

0.359

Gnomad AMR exome

AF:

0.371

Gnomad ASJ exome

AF:

0.139

Gnomad EAS exome

AF:

0.551

Gnomad FIN exome

AF:

0.174

Gnomad NFE exome

AF:

0.202

Gnomad OTH exome

AF:

0.246

GnomAD4 exome

AF:

0.229

AC:

334135

AN:

1461592

Hom.:

42507

Cov.:

AF XY:

0.229

AC XY:

166543

AN XY:

727102

show subpopulations

African (AFR)

AF:

0.378

AC:

12657

AN:

33480

American (AMR)

AF:

0.362

AC:

16200

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.139

AC:

3624

AN:

26134

East Asian (EAS)

AF:

0.551

AC:

21892

AN:

39700

South Asian (SAS)

AF:

0.292

AC:

25150

AN:

86254

European-Finnish (FIN)

AF:

0.179

AC:

9517

AN:

53150

Middle Eastern (MID)

AF:

0.206

AC:

1187

AN:

5768

European-Non Finnish (NFE)

AF:

0.206

AC:

229385

AN:

1112000

Other (OTH)

AF:

0.240

AC:

14523

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

16443

32886

49330

65773

82216

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8370

16740

25110

33480

41850

<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:

0.265

AC:

40331

AN:

152022

Hom.:

6065

Cov.:

AF XY:

0.267

AC XY:

19867

AN XY:

74292

show subpopulations

African (AFR)

AF:

0.360

AC:

14938

AN:

41464

American (AMR)

AF:

0.296

AC:

4526

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.139

AC:

483

AN:

3470

East Asian (EAS)

AF:

0.544

AC:

2796

AN:

5142

South Asian (SAS)

AF:

0.305

AC:

1468

AN:

4806

European-Finnish (FIN)

AF:

0.172

AC:

1821

AN:

10564

Middle Eastern (MID)

AF:

0.173

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.200

AC:

13582

AN:

67994

Other (OTH)

AF:

0.250

AC:

527

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1459

2918

4378

5837

7296

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

408

816

1224

1632

2040

<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:

0.228

Hom.:

12057

Bravo

AF:

0.282

Asia WGS

AF:

0.411

AC:

1430

AN:

3478

EpiCase

AF:

0.196

EpiControl

AF:

0.204

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

8.5

(source)

DANN

Benign

0.77

PhyloP100

0.12

PromoterAI

0.074

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=94/6

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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

Computational scores

Splicing

Publications

Other links and lift over