Genetic Variant NM_053050.5:c.10G>C (chr2-74472651-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_053050.5(MRPL53):c.10G>C(p.Ala4Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,884 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A4S) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

MRPL53
NM_053050.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.409

Variant links:

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]

MRPL53 links:

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

CCDC142 links:

ENSG00000286883 (HGNC:):

ENSG00000286883 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.11449492).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MRPL53	NM_053050.5 link	c.10G>C	p.Ala4Pro	missense_variant	Exon 1 of 3	ENST00000258105.8	NP_444278.1	Q96EL3
CCDC142	NM_001365575.2 link	c.*1895G>C		downstream_gene_variant		ENST00000393965.8	NP_001352504.1
CCDC142	NM_032779.4 link	c.*1895G>C		downstream_gene_variant			NP_116168.3	Q17RM4-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MRPL53	ENST00000258105.8 link	c.10G>C	p.Ala4Pro	missense_variant	Exon 1 of 3	1	NM_053050.5	ENSP00000258105.7		Q96EL3
CCDC142	ENST00000393965.8 link	c.*1895G>C		downstream_gene_variant		1	NM_001365575.2	ENSP00000377537.3		Q17RM4-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000342

AC:

AN:

1461884

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727240

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000450

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.020

T;T

Eigen

Benign

-0.75

Eigen_PC

Benign

-0.75

FATHMM_MKL

Benign

0.068

LIST_S2

Benign

0.54

T;T

M_CAP

Benign

0.023

MetaRNN

Benign

0.11

T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.0

L;.

PrimateAI

Benign

0.46

PROVEAN

Benign

-1.3

N;D

REVEL

Benign

0.035

Sift

Benign

0.21

T;D

Sift4G

Benign

0.20

T;D

Polyphen

0.23

B;.

Vest4

0.22

MutPred

0.36

Gain of relative solvent accessibility (P = 0.0479);Gain of relative solvent accessibility (P = 0.0479);

MVP

0.74

MPC

0.60

ClinPred

0.17

GERP RS

2.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.16

gMVP

0.34

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

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over