10-100986746-C-T

Variant names:

• chr10-100986746-C-T
• rs2863095
• NM_032112.3:c.468G>A

Variant summary

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.118
• Publications: 58 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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.527 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001394981.1. 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
	MRPL43	NM_032112.3	MANE Select	c.468G>A	p.Val156Val	synonymous	Exon 3 of 3	NP_115488.2
	MRPL43	NM_001437430.1		c.468G>A	p.Val156Val	synonymous	Exon 3 of 4	NP_001424359.1
	MRPL43	NM_001394981.1		c.465+3G>A		splice_region intron	N/A	NP_001381910.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRPL43	ENST00000318364.13	TSL:1 MANE Select	c.468G>A	p.Val156Val	synonymous	Exon 3 of 3	ENSP00000315948.8	Q8N983-4
	MRPL43	ENST00000318325.6	TSL:1	c.465+3G>A		splice_region intron	N/A	ENSP00000315364.2	Q8N983-1
	MRPL43	ENST00000299179.9	TSL:1	c.465+3G>A		splice_region intron	N/A	ENSP00000299179.5	Q8N983-2

Frequencies

GnomAD3 genomes AF: 0.265 AC: 40293 AN: 151904 Hom.: 6055 Cov.: 32

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

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.: 38 AF XY: 0.229 AC XY: 166543 AN XY: 727102

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

GnomAD4 genome AF: 0.265 AC: 40331 AN: 152022 Hom.: 6065 Cov.: 32 AF XY: 0.267 AC XY: 19867 AN XY: 74292

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: 51 AN: 294

European-Non Finnish (NFE) AF: 0.200 AC: 13582 AN: 67994

Other (OTH) AF: 0.250 AC: 527 AN: 2104

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	8.5
DANN	Benign	0.77
PhyloP100		0.12
PromoterAI		0.074	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=94/6	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2863095; hg19: chr10-102746503; COSMIC: COSV52966341; COSMIC: COSV52966341;