rs368616903

Variant names:

• chr3-179598751-C-T
• rs368616903
• NM_020409.3:c.326G>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_020409.3(MRPL47):​c.326G>A​(p.Arg109Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,458,998 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: MRPL47 NM_020409.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.25
• Publications: 0 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.38885543).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020409.3. 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
	MRPL47	NM_020409.3	MANE Select	c.326G>A	p.Arg109Lys	missense	Exon 4 of 7	NP_065142.2
	MRPL47	NM_177988.1		c.-5G>A		5_prime_UTR	Exon 3 of 6	NP_817125.1	Q9HD33-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRPL47	ENST00000476781.6	TSL:1 MANE Select	c.326G>A	p.Arg109Lys	missense	Exon 4 of 7	ENSP00000417602.1	Q9HD33-1
	MRPL47	ENST00000259038.6	TSL:1	c.266G>A	p.Arg89Lys	missense	Exon 4 of 7	ENSP00000259038.2	Q9HD33-2
	MRPL47	ENST00000392659.2	TSL:1	c.-5G>A		5_prime_UTR	Exon 3 of 6	ENSP00000376427.2	Q9HD33-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1458998 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 725872

African (AFR) AF: 0.00 AC: 0 AN: 33428

American (AMR) AF: 0.00 AC: 0 AN: 44688

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26044

East Asian (EAS) AF: 0.00 AC: 0 AN: 39632

South Asian (SAS) AF: 0.00 AC: 0 AN: 86194

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53298

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5754

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1109714

Other (OTH) AF: 0.0000166 AC: 1 AN: 60246

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.050	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.045	T
Eigen	Benign	0.018
Eigen_PC	Benign	0.15
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.85	T
M_CAP	Benign	0.0067	T
MetaRNN	Benign	0.39	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N
PhyloP100		2.2
PrimateAI	Pathogenic	0.79	T
PROVEAN	Benign	-0.90	N
REVEL	Benign	0.19
Sift	Benign	0.47	T
Sift4G	Benign	0.52	T
Polyphen		0.44	B
Vest4		0.27
MutPred		0.58		Gain of methylation at R109 (P = 0.0123)
MVP		0.80
MPC		0.19
ClinPred		0.31	T
GERP RS		6.2
Varity_R		0.26
gMVP		0.61
Mutation Taster		=73/27	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs368616903; hg19: chr3-179316539;