chr1-156738097-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_145729.3(MRPL24):​c.317G>A​(p.Gly106Glu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

MRPL24
NM_145729.3 missense

Scores

9
5
5

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.83
Variant links:
Genes affected
MRPL24 (HGNC:14037): (mitochondrial ribosomal protein L24) 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 which is more than twice the size of its E.coli counterpart (EcoL24). Sequence analysis identified two transcript variants that encode the same protein. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.826

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MRPL24NM_145729.3 linkc.317G>A p.Gly106Glu missense_variant Exon 4 of 6 ENST00000361531.6 NP_663781.1 Q96A35
MRPL24NM_024540.4 linkc.317G>A p.Gly106Glu missense_variant Exon 4 of 6 NP_078816.2 Q96A35
MRPL24XM_011509981.3 linkc.317G>A p.Gly106Glu missense_variant Exon 4 of 6 XP_011508283.1 Q96A35
MRPL24XM_011509982.3 linkc.317G>A p.Gly106Glu missense_variant Exon 4 of 6 XP_011508284.1 Q96A35

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MRPL24ENST00000361531.6 linkc.317G>A p.Gly106Glu missense_variant Exon 4 of 6 1 NM_145729.3 ENSP00000354525.2 Q96A35

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
Feb 05, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.317G>A (p.G106E) alteration is located in exon 4 (coding exon 3) of the MRPL24 gene. This alteration results from a G to A substitution at nucleotide position 317, causing the glycine (G) at amino acid position 106 to be replaced by a glutamic acid (E). 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
0.76
BayesDel_addAF
Pathogenic
0.45
D
BayesDel_noAF
Pathogenic
0.41
CADD
Pathogenic
26
DANN
Uncertain
1.0
DEOGEN2
Benign
0.31
T;T;T
Eigen
Pathogenic
0.87
Eigen_PC
Pathogenic
0.79
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Benign
0.84
.;T;T
M_CAP
Benign
0.018
T
MetaRNN
Pathogenic
0.83
D;D;D
MetaSVM
Uncertain
0.20
D
MutationAssessor
Pathogenic
4.0
H;H;.
PrimateAI
Uncertain
0.58
T
PROVEAN
Pathogenic
-6.4
D;D;D
REVEL
Uncertain
0.52
Sift
Benign
0.044
D;D;D
Sift4G
Uncertain
0.0030
D;D;D
Polyphen
1.0
D;D;.
Vest4
0.79
MutPred
0.49
Gain of solvent accessibility (P = 0.012);Gain of solvent accessibility (P = 0.012);Gain of solvent accessibility (P = 0.012);
MVP
0.88
MPC
1.0
ClinPred
1.0
D
GERP RS
5.4
Varity_R
0.85
gMVP
0.76

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.

Other links and lift over

hg19: chr1-156707889; API