11-1950951-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 1P and 0B. PP3

The NM_021134.4(MRPL23):c.70T>G(p.Phe24Val) variant causes a missense change. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 5)
• Consequence: MRPL23 NM_021134.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.41

Genes affected

MRPL23 (HGNC:10322): (mitochondrial ribosomal protein L23) 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. The gene is biallelically expressed, despite its location within a region of imprinted genes on chromosome 11. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.759

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MRPL23	NM_021134.4	c.70T>G	p.Phe24Val	missense_variant	2/5	ENST00000397298.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MRPL23	ENST00000397298.8	c.70T>G	p.Phe24Val	missense_variant	2/5	1	NM_021134.4	P1

Frequencies

GnomAD3 genomes Cov.: 5

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 5

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

Nov 23, 2021

The c.70T>G (p.F24V) alteration is located in exon 2 (coding exon 2) of the MRPL23 gene. This alteration results from a T to G substitution at nucleotide position 70, causing the phenylalanine (F) at amino acid position 24 to be replaced by a valine (V). 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	0.64
BayesDel_addAF	Uncertain	0.027	T
BayesDel_noAF	Benign	-0.20
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.064	T;T;T;T;T
Eigen	Uncertain	0.64
Eigen_PC	Uncertain	0.58
FATHMM_MKL	Uncertain	0.90	D
M_CAP	Benign	0.038	D
MetaRNN	Pathogenic	0.76	D;D;D;D;D
MetaSVM	Benign	-0.79	T
MutationAssessor	Uncertain	2.8	M;M;.;.;.
MutationTaster	Benign	1.0	D;D;D;D;D
PrimateAI	Uncertain	0.72	T
PROVEAN	Pathogenic	-6.3	D;D;D;D;D
REVEL	Uncertain	0.31
Sift	Uncertain	0.0020	D;D;D;D;D
Sift4G	Uncertain	0.0020	D;D;D;D;D
Polyphen		0.99	D;D;.;.;.
Vest4		0.76
MutPred		0.70		Loss of stability (P = 0.0706);Loss of stability (P = 0.0706);Loss of stability (P = 0.0706);Loss of stability (P = 0.0706);Loss of stability (P = 0.0706);
MVP		0.52
MPC		0.63
ClinPred		0.99	D
GERP RS		4.5
Varity_R		0.97
gMVP		0.63

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: chr11-1972181;