14-22834206-C-G

Position:

• chr14-22834206-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_180982.3(MRPL52):​c.254C>G​(p.Ala85Gly) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: MRPL52 NM_180982.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.31

Genes affected

MRPL52 (HGNC:16655): (mitochondrial ribosomal protein L52) 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 has no bacterial homolog. Multiple transcript variants encoding different protein isoforms were identified through sequence analysis. [provided by RefSeq, Jul 2008]

MRPL52 (HGNC:):

ACMG classification

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=0.17382753).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MRPL52	NM_180982.3	c.254C>G	p.Ala85Gly	missense_variant	5/5	ENST00000397496.7	NP_851313.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MRPL52	ENST00000397496.7	c.254C>G	p.Ala85Gly	missense_variant	5/5	2	NM_180982.3	ENSP00000380633.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000480 Hom.: 0

ExAC AF: 0.00000824 AC: 1

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 03, 2024

The c.257C>G (p.A86G) alteration is located in exon 5 (coding exon 5) of the MRPL52 gene. This alteration results from a C to G substitution at nucleotide position 257, causing the alanine (A) at amino acid position 86 to be replaced by a glycine (G). 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	Benign	0.15
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.025	T;.;.;.;.;.
Eigen	Uncertain	0.31
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.71	T;T;.;.;T;T
M_CAP	Benign	0.051	D
MetaRNN	Benign	0.17	T;T;T;T;T;T
MetaSVM	Benign	-0.55	T
MutationAssessor	Uncertain	2.3	M;.;.;.;.;.
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-1.4	N;N;N;N;D;N
REVEL	Benign	0.035
Sift	Benign	0.33	T;T;T;T;D;T
Sift4G	Benign	0.38	T;T;T;T;T;T
Polyphen		0.010	B;.;.;.;.;.
Vest4		0.22
MutPred		0.37		Loss of MoRF binding (P = 0.1292);.;.;.;.;.;
MVP		0.19
MPC		0.34
ClinPred		0.77	D
GERP RS		5.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.21
gMVP		0.31

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs369393430; hg19: chr14-23303415;