rs10513762

Positions:

• chr3-179588987-C-T

Variant summary

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

The ENST00000476781.6(MRPL47):​c.638G>A​(p.Arg213His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0848 in 1,609,990 control chromosomes in the GnomAD database, including 6,587 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.091 (673 hom., cov: 32)
  • Exomes 𝑓: 0.084 (5914 hom.)
• Consequence: MRPL47 ENST00000476781.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.09

Genes affected

MRPL47 (HGNC:16652): (mitochondrial ribosomal protein L47) 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 is immediately adjacent to the gene for BAF complex 53 kDa subunit protein a (BAF53a), in a tail-to-tail orientation. Two transcript variants encoding different protein isoforms have been identified. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0016101599).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.159 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MRPL47	NM_020409.3	c.638G>A	p.Arg213His	missense_variant	7/7	ENST00000476781.6	NP_065142.2
MRPL47	NM_177988.1	c.308G>A	p.Arg103His	missense_variant	6/6		NP_817125.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MRPL47	ENST00000476781.6	c.638G>A	p.Arg213His	missense_variant	7/7	1	NM_020409.3	ENSP00000417602	P1
MRPL47	ENST00000259038.6	c.578G>A	p.Arg193His	missense_variant	7/7	1		ENSP00000259038
MRPL47	ENST00000392659.2	c.308G>A	p.Arg103His	missense_variant	6/6	1		ENSP00000376427

Frequencies

GnomAD3 genomes AF: 0.0906 AC: 13767 AN: 152004 Hom.: 670 Cov.: 32

Gnomad AFR AF: 0.0957

Gnomad AMI AF: 0.123

Gnomad AMR AF: 0.123

Gnomad ASJ AF: 0.0638

Gnomad EAS AF: 0.111

Gnomad SAS AF: 0.170

Gnomad FIN AF: 0.0810

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.0755

Gnomad OTH AF: 0.0881

GnomAD3 exomes AF: 0.103 AC: 25581 AN: 248496 Hom.: 1557 AF XY: 0.103 AC XY: 13899 AN XY: 134430

Gnomad AFR exome AF: 0.0949

Gnomad AMR exome AF: 0.170

Gnomad ASJ exome AF: 0.0637

Gnomad EAS exome AF: 0.102

Gnomad SAS exome AF: 0.164

Gnomad FIN exome AF: 0.0841

Gnomad NFE exome AF: 0.0754

Gnomad OTH exome AF: 0.0929

GnomAD4 exome AF: 0.0842 AC: 122714 AN: 1457868 Hom.: 5914 Cov.: 31 AF XY: 0.0861 AC XY: 62441 AN XY: 725240

Gnomad4 AFR exome AF: 0.0979

Gnomad4 AMR exome AF: 0.163

Gnomad4 ASJ exome AF: 0.0632

Gnomad4 EAS exome AF: 0.125

Gnomad4 SAS exome AF: 0.163

Gnomad4 FIN exome AF: 0.0824

Gnomad4 NFE exome AF: 0.0740

Gnomad4 OTH exome AF: 0.0831

GnomAD4 genome AF: 0.0907 AC: 13792 AN: 152122 Hom.: 673 Cov.: 32 AF XY: 0.0937 AC XY: 6965 AN XY: 74360

Gnomad4 AFR AF: 0.0960

Gnomad4 AMR AF: 0.124

Gnomad4 ASJ AF: 0.0638

Gnomad4 EAS AF: 0.111

Gnomad4 SAS AF: 0.169

Gnomad4 FIN AF: 0.0810

Gnomad4 NFE AF: 0.0755

Gnomad4 OTH AF: 0.0867

Alfa AF: 0.0809 Hom.: 1527

Bravo AF: 0.0917

TwinsUK AF: 0.0720 AC: 267

ALSPAC AF: 0.0690 AC: 266

ESP6500AA AF: 0.0921 AC: 406

ESP6500EA AF: 0.0779 AC: 670

ExAC AF: 0.100 AC: 12180

Asia WGS AF: 0.114 AC: 396 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.67	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	8.7
DANN	Benign	0.83
DEOGEN2	Benign	0.081	T;.;.
Eigen	Benign	-0.72
Eigen_PC	Benign	-0.83
FATHMM_MKL	Benign	0.25	N
LIST_S2	Benign	0.85	T;T;D
MetaRNN	Benign	0.0016	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.1	L;.;.
MutationTaster	Benign	1.0	P;P;P
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-2.3	N;N;D
REVEL	Benign	0.16
Sift	Benign	0.47	T;T;T
Sift4G	Benign	0.57	T;T;T
Polyphen		0.97	D;D;.
Vest4		0.064
MPC		0.25
ClinPred		0.021	T
GERP RS		-2.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.058
gMVP		0.67

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: rs10513762; hg19: chr3-179306775; COSMIC: COSV52022659; COSMIC: COSV52022659;