2-74472225-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_053050.5(MRPL53):​c.233G>A​(p.Gly78Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

MRPL53
NM_053050.5 missense

Scores

1
10
8

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.18
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]
CCDC142 (HGNC:25889): (coiled-coil domain containing 142)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MRPL53NM_053050.5 linkc.233G>A p.Gly78Asp missense_variant Exon 3 of 3 ENST00000258105.8 NP_444278.1 Q96EL3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MRPL53ENST00000258105.8 linkc.233G>A p.Gly78Asp missense_variant Exon 3 of 3 1 NM_053050.5 ENSP00000258105.7 Q96EL3

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Oct 03, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.233G>A (p.G78D) alteration is located in exon 3 (coding exon 3) of the MRPL53 gene. This alteration results from a G to A substitution at nucleotide position 233, causing the glycine (G) at amino acid position 78 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.93
BayesDel_addAF
Uncertain
0.044
T
BayesDel_noAF
Benign
-0.17
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.18
T
Eigen
Uncertain
0.36
Eigen_PC
Uncertain
0.32
FATHMM_MKL
Benign
0.13
N
LIST_S2
Benign
0.84
T
M_CAP
Benign
0.037
D
MetaRNN
Uncertain
0.66
D
MetaSVM
Benign
-0.74
T
MutationAssessor
Uncertain
2.3
M
PrimateAI
Uncertain
0.52
T
PROVEAN
Uncertain
-2.7
D
REVEL
Benign
0.28
Sift
Uncertain
0.029
D
Sift4G
Uncertain
0.012
D
Polyphen
0.99
D
Vest4
0.54
MutPred
0.72
Gain of relative solvent accessibility (P = 0.0479);
MVP
0.50
MPC
1.4
ClinPred
0.98
D
GERP RS
4.1
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.88
gMVP
0.51

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-74699352; API