7-42932391-CG-TC

Variant names:

• chr7-42932391-CG-TC
• NM_031903.3:c.5_6delCGinsTC
• MRPL32 p.Ala2Val

Variant summary

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

The NM_031903.3(MRPL32):​c.5_6delCGinsTC​(p.Ala2Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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: 31)
• Consequence: MRPL32 NM_031903.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.719
• Publications: 0 publications found

Genes affected

MRPL32 (HGNC:14035): (mitochondrial ribosomal protein L32) 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 that belongs to the L32 ribosomal protein family. A pseudogene corresponding to this gene is found on chromosome Xp. [provided by RefSeq, Jul 2008]

PSMA2 (HGNC:9531): (proteasome 20S subunit alpha 2) The proteasome is a multicatalytic proteinase complex with a highly ordered ring-shaped 20S core structure. The core structure is composed of 4 rings of 28 non-identical subunits; 2 rings are composed of 7 alpha subunits and 2 rings are composed of 7 beta subunits. Proteasomes are distributed throughout eukaryotic cells at a high concentration and cleave peptides in an ATP/ubiquitin-dependent process in a non-lysosomal pathway. An essential function of a modified proteasome, the immunoproteasome, is the processing of class I MHC peptides. This gene encodes a member of the peptidase T1A family, that is a 20S core alpha subunit. [provided by RefSeq, Jul 2008]

ENSG00000256646 (HGNC:):

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031903.3. 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
	MRPL32	NM_031903.3	MANE Select	c.5_6delCGinsTC	p.Ala2Val	missense	N/A	NP_114109.1	Q9BYC8
	MRPL32	NR_156497.1		n.16_17delCGinsTC		non_coding_transcript_exon	Exon 1 of 4
	PSMA2	NM_002787.5	MANE Select	c.-234_-233delCGinsGA		upstream_gene	N/A	NP_002778.1	P25787

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRPL32	ENST00000223324.3	TSL:1 MANE Select	c.5_6delCGinsTC	p.Ala2Val	missense	N/A	ENSP00000223324.2	Q9BYC8
	MRPL32	ENST00000900012.1		c.5_6delCGinsTC	p.Ala2Val	missense	N/A	ENSP00000570071.1
	MRPL32	ENST00000921963.1		c.5_6delCGinsTC	p.Ala2Val	missense	N/A	ENSP00000592022.1

Frequencies

GnomAD3 genomes Cov.: 31

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

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.72

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: chr7-42971990;