NM_053050.5:c.107C>G

Variant names:

• chr2-74472456-G-C
• rs749654917
• NM_053050.5:c.107C>G

Variant summary

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

The NM_053050.5(MRPL53):​c.107C>G​(p.Thr36Arg) 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. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T36M) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MRPL53 NM_053050.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.46
• Publications: 0 publications found

Genes affected

MRPL53 (HGNC:16684): (mitochondrial ribosomal protein L53) 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. A pseudogene corresponding to this gene is found on chromosome 1p. [provided by RefSeq, Jul 2008]

CCDC142 (HGNC:25889): (coiled-coil domain containing 142)

ENSG00000286883 (HGNC:):

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=0.17396241).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_053050.5. 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
	MRPL53	NM_053050.5	MANE Select	c.107C>G	p.Thr36Arg	missense	Exon 2 of 3	NP_444278.1	Q96EL3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRPL53	ENST00000258105.8	TSL:1 MANE Select	c.107C>G	p.Thr36Arg	missense	Exon 2 of 3	ENSP00000258105.7	Q96EL3
	MRPL53	ENST00000906488.1		c.107C>G	p.Thr36Arg	missense	Exon 2 of 3	ENSP00000576547.1
	MRPL53	ENST00000409710.1	TSL:2	c.92+113C>G		intron	N/A	ENSP00000386920.1	B9A051

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

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	0.15
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	19
DANN	Benign	0.74
DEOGEN2	Benign	0.0033	T
Eigen	Benign	-0.73
Eigen_PC	Benign	-0.53
FATHMM_MKL	Benign	0.33	N
LIST_S2	Benign	0.090	T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.69	N
PhyloP100		2.5
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-0.38	N
REVEL	Benign	0.083
Sift	Benign	0.35	T
Sift4G	Benign	0.37	T
Polyphen		0.0010	B
Vest4		0.47
MutPred		0.32		Loss of sheet (P = 0.0037)
MVP		0.33
MPC		0.59
ClinPred		0.26	T
GERP RS		3.8
PromoterAI		-0.048	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.19
gMVP		0.22
Mutation Taster		=88/12	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs749654917; hg19: chr2-74699583;