Genetic Variant MRPL43:p.Val156Val (chr10-100986746-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001394981.1(MRPL43):c.465+3G>A variant causes a splice region, intron 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. 1/1 splice prediction tools predict no significant impact on normal splicing. 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_001394981.1 splice_region, intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.118

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 made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

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

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

GnomAD3 exomes

AF:

0.268

AC:

67393

AN:

251048

Hom.:

10604

AF XY:

0.262

AC XY:

35514

AN XY:

135754

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 SAS exome

AF:

0.294

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

Gnomad4 AFR exome

AF:

0.378

Gnomad4 AMR exome

AF:

0.362

Gnomad4 ASJ exome

AF:

0.139

Gnomad4 EAS exome

AF:

0.551

Gnomad4 SAS exome

AF:

0.292

Gnomad4 FIN exome

AF:

0.179

Gnomad4 NFE exome

AF:

0.206

Gnomad4 OTH exome

AF:

0.240

GnomAD4 genome

AF:

0.265

AC:

40331

AN:

152022

Hom.:

6065

Cov.:

AF XY:

0.267

AC XY:

19867

AN XY:

74292

show subpopulations

Gnomad4 AFR

AF:

0.360

Gnomad4 AMR

AF:

0.296

Gnomad4 ASJ

AF:

0.139

Gnomad4 EAS

AF:

0.544

Gnomad4 SAS

AF:

0.305

Gnomad4 FIN

AF:

0.172

Gnomad4 NFE

AF:

0.200

Gnomad4 OTH

AF:

0.250

Alfa

AF:

0.213

Hom.:

6755

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

DANN

Benign

0.77

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over