3-179604597-A-C

Position:

• chr3-179604597-A-C

Variant summary

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

The NM_020409.3(MRPL47):​c.28T>G​(p.Cys10Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.086 in 1,614,094 control chromosomes in the GnomAD database, including 6,803 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 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 (689 hom., cov: 33)
  • Exomes 𝑓: 0.085 (6114 hom.)
• Consequence: MRPL47 NM_020409.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.61

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=0.0014838278).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.164 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MRPL47	NM_020409.3	c.28T>G	p.Cys10Gly	missense_variant	1/7	ENST00000476781.6	NP_065142.2
MRPL47	NM_177988.1	c.-157T>G		5_prime_UTR_variant	1/6		NP_817125.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MRPL47	ENST00000476781.6	c.28T>G	p.Cys10Gly	missense_variant	1/7	1	NM_020409.3	ENSP00000417602	P1
MRPL47	ENST00000259038.6	c.28T>G	p.Cys10Gly	missense_variant	1/7	1		ENSP00000259038
MRPL47	ENST00000392659.2	c.-157T>G		5_prime_UTR_variant	1/6	1		ENSP00000376427

Frequencies

GnomAD3 genomes AF: 0.0910 AC: 13842 AN: 152168 Hom.: 686 Cov.: 33

Gnomad AFR AF: 0.0956

Gnomad AMI AF: 0.123

Gnomad AMR AF: 0.124

Gnomad ASJ AF: 0.0640

Gnomad EAS AF: 0.112

Gnomad SAS AF: 0.174

Gnomad FIN AF: 0.0809

Gnomad MID AF: 0.0796

Gnomad NFE AF: 0.0759

Gnomad OTH AF: 0.0894

GnomAD3 exomes AF: 0.104 AC: 26214 AN: 251370 Hom.: 1626 AF XY: 0.105 AC XY: 14284 AN XY: 135876

Gnomad AFR exome AF: 0.0951

Gnomad AMR exome AF: 0.171

Gnomad ASJ exome AF: 0.0646

Gnomad EAS exome AF: 0.102

Gnomad SAS exome AF: 0.171

Gnomad FIN exome AF: 0.0839

Gnomad NFE exome AF: 0.0757

Gnomad OTH exome AF: 0.0951

GnomAD4 exome AF: 0.0854 AC: 124869 AN: 1461808 Hom.: 6114 Cov.: 32 AF XY: 0.0875 AC XY: 63651 AN XY: 727204

Gnomad4 AFR exome AF: 0.0983

Gnomad4 AMR exome AF: 0.164

Gnomad4 ASJ exome AF: 0.0645

Gnomad4 EAS exome AF: 0.126

Gnomad4 SAS exome AF: 0.170

Gnomad4 FIN exome AF: 0.0824

Gnomad4 NFE exome AF: 0.0748

Gnomad4 OTH exome AF: 0.0844

GnomAD4 genome AF: 0.0911 AC: 13867 AN: 152286 Hom.: 689 Cov.: 33 AF XY: 0.0942 AC XY: 7012 AN XY: 74458

Gnomad4 AFR AF: 0.0960

Gnomad4 AMR AF: 0.124

Gnomad4 ASJ AF: 0.0640

Gnomad4 EAS AF: 0.112

Gnomad4 SAS AF: 0.174

Gnomad4 FIN AF: 0.0809

Gnomad4 NFE AF: 0.0760

Gnomad4 OTH AF: 0.0880

Alfa AF: 0.0816 Hom.: 1544

Bravo AF: 0.0920

TwinsUK AF: 0.0723 AC: 268

ALSPAC AF: 0.0695 AC: 268

ESP6500AA AF: 0.0924 AC: 407

ESP6500EA AF: 0.0785 AC: 675

ExAC AF: 0.102 AC: 12341

Asia WGS AF: 0.118 AC: 411 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	-0.57	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	20
DANN	Benign	0.65
DEOGEN2	Benign	0.0072	T;.
Eigen	Benign	-0.45
Eigen_PC	Benign	-0.41
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.44	T;T
MetaRNN	Benign	0.0015	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.1	M;M
MutationTaster	Benign	1.0	P;P;P
PrimateAI	Uncertain	0.48	T
PROVEAN	Benign	-1.4	N;N
REVEL	Benign	0.066
Sift	Benign	0.26	T;T
Sift4G	Benign	0.27	T;T
Polyphen		0.0020	B;B
Vest4		0.50
MPC		0.17
ClinPred		0.035	T
GERP RS		5.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.42
gMVP		0.62

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs2339844; hg19: chr3-179322385; COSMIC: COSV52019701; COSMIC: COSV52019701;