chr1-156738097-C-T

Variant names:

• chr1-156738097-C-T
• NM_145729.3:c.317G>A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.83

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]

ACMG classification

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
MRPL24	NM_145729.3	c.317G>A	p.Gly106Glu	missense_variant	Exon 4 of 6	ENST00000361531.6	NP_663781.1
MRPL24	NM_024540.4	c.317G>A	p.Gly106Glu	missense_variant	Exon 4 of 6		NP_078816.2
MRPL24	XM_011509981.3	c.317G>A	p.Gly106Glu	missense_variant	Exon 4 of 6		XP_011508283.1
MRPL24	XM_011509982.3	c.317G>A	p.Gly106Glu	missense_variant	Exon 4 of 6		XP_011508284.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MRPL24	ENST00000361531.6	c.317G>A	p.Gly106Glu	missense_variant	Exon 4 of 6	1	NM_145729.3	ENSP00000354525.2

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

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;