10-100986474-C-T

Position:

• chr10-100986474-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032112.3(MRPL43):​c.*260G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.403 in 1,535,994 control chromosomes in the GnomAD database, including 131,149 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 0.34 (10337 hom., cov: 32)
  • Exomes 𝑓: 0.41 (120812 hom.)
• Consequence: MRPL43 NM_032112.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.186

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.436 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MRPL43	NM_032112.3	c.*260G>A		3_prime_UTR_variant	3/3	ENST00000318364.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MRPL43	ENST00000318364.13	c.*260G>A		3_prime_UTR_variant	3/3	1	NM_032112.3	P1

Frequencies

GnomAD3 genomes AF: 0.338 AC: 51406 AN: 151954 Hom.: 10337 Cov.: 32

Gnomad AFR AF: 0.132

Gnomad AMI AF: 0.540

Gnomad AMR AF: 0.390

Gnomad ASJ AF: 0.455

Gnomad EAS AF: 0.0684

Gnomad SAS AF: 0.390

Gnomad FIN AF: 0.455

Gnomad MID AF: 0.554

Gnomad NFE AF: 0.440

Gnomad OTH AF: 0.368

GnomAD4 exome AF: 0.410 AC: 567310 AN: 1383922 Hom.: 120812 Cov.: 41 AF XY: 0.411 AC XY: 280362 AN XY: 682296

Gnomad4 AFR exome AF: 0.116

Gnomad4 AMR exome AF: 0.367

Gnomad4 ASJ exome AF: 0.454

Gnomad4 EAS exome AF: 0.0518

Gnomad4 SAS exome AF: 0.400

Gnomad4 FIN exome AF: 0.471

Gnomad4 NFE exome AF: 0.430

Gnomad4 OTH exome AF: 0.378

GnomAD4 genome AF: 0.338 AC: 51402 AN: 152072 Hom.: 10337 Cov.: 32 AF XY: 0.339 AC XY: 25221 AN XY: 74336

Gnomad4 AFR AF: 0.132

Gnomad4 AMR AF: 0.390

Gnomad4 ASJ AF: 0.455

Gnomad4 EAS AF: 0.0686

Gnomad4 SAS AF: 0.392

Gnomad4 FIN AF: 0.455

Gnomad4 NFE AF: 0.440

Gnomad4 OTH AF: 0.365

Alfa AF: 0.412 Hom.: 16343

Bravo AF: 0.319

Asia WGS AF: 0.226 AC: 786 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	10
DANN	Benign	0.59

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

LitVar

Other links and lift over

dbSNP: rs7184; hg19: chr10-102746231; COSMIC: COSV52972447; COSMIC: COSV52972447;