11-1956275-CG-AA

Variant names:

• chr11-1956275-CG-AA
• NM_021134.4:c.317_318delCGinsAA
• MRPL23 p.Thr106Lys

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_021134.4(MRPL23):​c.317_318delCGinsAA​(p.Thr106Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T106M) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 17)
• Consequence: MRPL23 NM_021134.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.455
• 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_021134.4. 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.317_318delCGinsAA	p.Thr106Lys	missense	N/A	NP_066957.3
	MRPL23	NM_001400172.1		c.182_183delCGinsAA	p.Thr61Lys	missense	N/A	NP_001387101.1
	MRPL23	NM_001400174.1		c.*52_*53delCGinsAA		3_prime_UTR	Exon 6 of 6	NP_001387103.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRPL23	ENST00000397298.8	TSL:1 MANE Select	c.317_318delCGinsAA	p.Thr106Lys	missense	N/A	ENSP00000380466.3	Q16540
	MRPL23	ENST00000924183.1		c.473_474delCGinsAA	p.Thr158Lys	missense	N/A	ENSP00000594242.1
	MRPL23	ENST00000869798.1		c.323_324delCGinsAA	p.Thr108Lys	missense	N/A	ENSP00000539857.1

Frequencies

GnomAD3 genomes Cov.: 17

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 17

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.46

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr11-1977505;