10-100986474-C-T

Variant names:

• chr10-100986474-C-T
• rs7184
• ENST00000493646.1:n.699G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000493646.1(MRPL43):​n.699G>A variant causes a non coding transcript exon 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 ENST00000493646.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.186
• Publications: 17 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
MRPL43	NM_032112.3	c.*260G>A		3_prime_UTR_variant	Exon 3 of 3	ENST00000318364.13	NP_115488.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MRPL43	ENST00000318364.13	c.*260G>A		3_prime_UTR_variant	Exon 3 of 3	1	NM_032112.3	ENSP00000315948.8

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

African (AFR) AF: 0.116 AC: 3524 AN: 30426

American (AMR) AF: 0.367 AC: 11520 AN: 31404

Ashkenazi Jewish (ASJ) AF: 0.454 AC: 11134 AN: 24502

East Asian (EAS) AF: 0.0518 AC: 1846 AN: 35656

South Asian (SAS) AF: 0.400 AC: 30642 AN: 76698

European-Finnish (FIN) AF: 0.471 AC: 22505 AN: 47778

Middle Eastern (MID) AF: 0.467 AC: 2623 AN: 5612

European-Non Finnish (NFE) AF: 0.430 AC: 461800 AN: 1074458

Other (OTH) AF: 0.378 AC: 21716 AN: 57388

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

African (AFR) AF: 0.132 AC: 5463 AN: 41488

American (AMR) AF: 0.390 AC: 5964 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.455 AC: 1581 AN: 3472

East Asian (EAS) AF: 0.0686 AC: 355 AN: 5178

South Asian (SAS) AF: 0.392 AC: 1891 AN: 4828

European-Finnish (FIN) AF: 0.455 AC: 4801 AN: 10544

Middle Eastern (MID) AF: 0.541 AC: 159 AN: 294

European-Non Finnish (NFE) AF: 0.440 AC: 29926 AN: 67964

Other (OTH) AF: 0.365 AC: 771 AN: 2114

Alfa AF: 0.389 Hom.: 28065

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
PhyloP100		0.19
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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