rs10513762

Variant names:

• chr3-179588987-C-T
• rs10513762
• NM_020409.3:c.638G>A

Variant summary

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

The NM_020409.3(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. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.091 (673 hom., cov: 32)
  • Exomes 𝑓: 0.084 (5914 hom.)
• Consequence: MRPL47 NM_020409.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.09
• Publications: 34 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
MRPL47	NM_020409.3	c.638G>A	p.Arg213His	missense_variant	Exon 7 of 7	ENST00000476781.6	NP_065142.2
MRPL47	NM_177988.1	c.308G>A	p.Arg103His	missense_variant	Exon 6 of 6		NP_817125.1

Ensembl

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

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

GnomAD2 exomes AF: 0.103 AC: 25581 AN: 248496 AF XY: 0.103

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 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

African (AFR) AF: 0.0979 AC: 3248 AN: 33164

American (AMR) AF: 0.163 AC: 7158 AN: 43868

Ashkenazi Jewish (ASJ) AF: 0.0632 AC: 1643 AN: 25978

East Asian (EAS) AF: 0.125 AC: 4964 AN: 39634

South Asian (SAS) AF: 0.163 AC: 13924 AN: 85642

European-Finnish (FIN) AF: 0.0824 AC: 4394 AN: 53338

Middle Eastern (MID) AF: 0.0446 AC: 256 AN: 5736

European-Non Finnish (NFE) AF: 0.0740 AC: 82127 AN: 1110332

Other (OTH) AF: 0.0831 AC: 5000 AN: 60176

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

African (AFR) AF: 0.0960 AC: 3985 AN: 41494

American (AMR) AF: 0.124 AC: 1888 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.0638 AC: 221 AN: 3466

East Asian (EAS) AF: 0.111 AC: 576 AN: 5180

South Asian (SAS) AF: 0.169 AC: 816 AN: 4826

European-Finnish (FIN) AF: 0.0810 AC: 857 AN: 10584

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.0755 AC: 5131 AN: 67988

Other (OTH) AF: 0.0867 AC: 183 AN: 2110

Alfa AF: 0.0819 Hom.: 2755

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;.;.
PhyloP100		1.1
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
Mutation Taster		=97/3	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: rs10513762; hg19: chr3-179306775; COSMIC: COSV52022659; COSMIC: COSV52022659;