12-93501189-CGT-TGC

Variant names:

• chr12-93501189-CGT-TGC
• NM_014050.4:c.397_399delCGTinsTGC
• MRPL42 p.Arg133Cys

Variant summary

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

The NM_014050.4(MRPL42):​c.397_399delCGTinsTGC​(p.Arg133Cys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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.

• Frequency: Genomes: not found (cov: 33)
• Consequence: MRPL42 NM_014050.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.08
• Publications: 0 publications found

Genes affected

MRPL42 (HGNC:14493): (mitochondrial ribosomal protein L42) 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 protein identified as belonging to both the 28S and the 39S subunits. Alternative splicing results in multiple transcript variants. Pseudogenes corresponding to this gene are found on chromosomes 4q, 6p, 6q, 7p, and 15q. [provided by RefSeq, May 2011]

SOCS2-AS1 (HGNC:27054): (SOCS2 antisense RNA 1)

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014050.4. 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
	MRPL42	NM_014050.4	MANE Select	c.397_399delCGTinsTGC	p.Arg133Cys	missense	N/A	NP_054769.1	Q9Y6G3
	MRPL42	NM_172177.5		c.397_399delCGTinsTGC	p.Arg133Cys	missense	N/A	NP_751917.1	Q9Y6G3
	MRPL42	NR_038159.2		n.555_557delCGTinsTGC		non_coding_transcript_exon	Exon 7 of 7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRPL42	ENST00000549982.6	TSL:1 MANE Select	c.397_399delCGTinsTGC	p.Arg133Cys	missense	N/A	ENSP00000449884.1	Q9Y6G3
	MRPL42	ENST00000358678.7	TSL:1	n.*346_*348delCGTinsTGC		non_coding_transcript_exon	Exon 7 of 7	ENSP00000351506.3	J3KP21
	MRPL42	ENST00000358678.7	TSL:1	n.*346_*348delCGTinsTGC		3_prime_UTR	Exon 7 of 7	ENSP00000351506.3	J3KP21

Frequencies

GnomAD3 genomes Cov.: 33

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

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		4.1

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: chr12-93894965;