NM_020409.3:c.748G>T

Variant names:

• chr3-179588877-C-A
• rs762650586
• NM_020409.3:c.748G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_020409.3(MRPL47):​c.748G>T​(p.Val250Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. V250I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MRPL47 NM_020409.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.819
• Publications: 1 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17691305).

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.748G>T	p.Val250Phe	missense	Exon 7 of 7	NP_065142.2
	MRPL47	NM_177988.1		c.418G>T	p.Val140Phe	missense	Exon 6 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.748G>T	p.Val250Phe	missense	Exon 7 of 7	ENSP00000417602.1	Q9HD33-1
	MRPL47	ENST00000259038.6	TSL:1	c.688G>T	p.Val230Phe	missense	Exon 7 of 7	ENSP00000259038.2	Q9HD33-2
	MRPL47	ENST00000392659.2	TSL:1	c.418G>T	p.Val140Phe	missense	Exon 6 of 6	ENSP00000376427.2	Q9HD33-3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1460802 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 726722

African (AFR) AF: 0.00 AC: 0 AN: 33398

American (AMR) AF: 0.00 AC: 0 AN: 44526

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26096

East Asian (EAS) AF: 0.00 AC: 0 AN: 39640

South Asian (SAS) AF: 0.00 AC: 0 AN: 86142

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53388

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5730

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111558

Other (OTH) AF: 0.00 AC: 0 AN: 60324

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0036	T
Eigen	Benign	-0.31
Eigen_PC	Benign	-0.41
FATHMM_MKL	Benign	0.30	N
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	1.8	L
PhyloP100		0.82
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.38	N
REVEL	Benign	0.078
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.014	D
Polyphen		0.96	D
Vest4		0.18
MutPred		0.50		Loss of stability (P = 0.0491)
MVP		0.48
MPC		0.45
ClinPred		0.69	D
GERP RS		3.3
Varity_R		0.078
gMVP		0.77
Mutation Taster		=88/12	polymorphism

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: rs762650586; hg19: chr3-179306665;