chr11-1950976-G-A

Variant names:

• chr11-1950976-G-A
• NM_021134.4:c.95G>A

Variant summary

Our verdict is Uncertain significance. The variant received 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
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001400172.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRPL23	NM_021134.4	MANE Select	c.95G>A	p.Gly32Asp	missense	Exon 2 of 5	NP_066957.3
	MRPL23	NM_001400172.1		c.-41G>A		5_prime_UTR_premature_start_codon_gain	Exon 2 of 5	NP_001387101.1
	MRPL23	NM_001400176.1		c.95G>A	p.Gly32Asp	missense	Exon 2 of 7	NP_001387105.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRPL23	ENST00000397298.8	TSL:1 MANE Select	c.95G>A	p.Gly32Asp	missense	Exon 2 of 5	ENSP00000380466.3	Q16540
	MRPL23	ENST00000924183.1		c.95G>A	p.Gly32Asp	missense	Exon 2 of 5	ENSP00000594242.1
	MRPL23	ENST00000397297.7	TSL:2	c.95G>A	p.Gly32Asp	missense	Exon 2 of 6	ENSP00000380465.3	A8MYK1

Frequencies

GnomAD3 genomes Cov.: 6

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 6

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.048	D
MetaRNN	Uncertain	0.53	D
MetaSVM	Benign	-0.88	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		7.9
PrimateAI	Uncertain	0.72	T
PROVEAN	Uncertain	-2.7	D
REVEL	Uncertain	0.31
Sift	Benign	0.34	T
Sift4G	Benign	0.15	T
Polyphen		1.0	D
Vest4		0.68
MutPred		0.43		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
Mutation Taster		=65/35	polymorphism

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

Other links and lift over

hg19: chr11-1972206;