chr11-1950976-G-A

Position:

• chr11-1950976-G-A

Variant summary

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

The NM_001400172.1(MRPL23):​c.-41G>A variant causes a 5 prime UTR premature start codon gain change involving the alteration of a conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 6)
• Consequence: MRPL23 NM_001400172.1 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.94

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 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MRPL23	NM_021134.4	c.95G>A	p.Gly32Asp	missense_variant	2/5	ENST00000397298.8	NP_066957.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MRPL23	ENST00000397298.8	c.95G>A	p.Gly32Asp	missense_variant	2/5	1	NM_021134.4	ENSP00000380466.3

Frequencies

GnomAD3 genomes Cov.: 6

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 6

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

Aug 26, 2024

The c.95G>A (p.G32D) alteration is located in exon 2 (coding exon 2) of the MRPL23 gene. This alteration results from a G to A substitution at nucleotide position 95, causing the glycine (G) at amino acid position 32 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	0.79
BayesDel_addAF	Uncertain	0.042	T
BayesDel_noAF	Benign	-0.18
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.025	T;T;T;T;T
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.91	.;D;D;D;D
M_CAP	Benign	0.048	D
MetaRNN	Uncertain	0.53	D;D;D;D;D
MetaSVM	Benign	-0.88	T
MutationAssessor	Uncertain	2.4	M;M;.;.;.
PrimateAI	Uncertain	0.72	T
PROVEAN	Uncertain	-2.7	D;D;D;D;D
REVEL	Uncertain	0.31
Sift	Benign	0.34	T;T;T;T;T
Sift4G	Benign	0.15	T;T;D;T;T
Polyphen		1.0	D;D;.;.;.
Vest4		0.68
MutPred		0.43		Loss of MoRF binding (P = 0.081);Loss of MoRF binding (P = 0.081);Loss of MoRF binding (P = 0.081);Loss of MoRF binding (P = 0.081);Loss of MoRF binding (P = 0.081);
MVP		0.58
MPC		0.79
ClinPred		0.97	D
GERP RS		4.5
Varity_R		0.55
gMVP		0.49

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: chr11-1972206;