12-109052733-CGC-TTG

Variant names:

• chr12-109052733-CGC-TTG
• NM_032663.5:c.55_57delCGCinsTTG
• USP30 p.Arg19Leu

Variant summary

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

The NM_032663.5(USP30):​c.55_57delCGCinsTTG​(p.Arg19Leu) 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. R19P) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: USP30 NM_032663.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.08
• Publications: 0 publications found

Genes affected

USP30 (HGNC:20065): (ubiquitin specific peptidase 30) USP30, a member of the ubiquitin-specific protease family (see USP1, MIM 603478), is a novel mitochondrial deubiquitinating (DUB) enzyme (Nakamura and Hirose, 2008 [PubMed 18287522]).[supplied by OMIM, Dec 2008]

USP30-AS1 (HGNC:40909): (USP30 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_032663.5. 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
	USP30	NM_032663.5	MANE Select	c.55_57delCGCinsTTG	p.Arg19Leu	missense	N/A	NP_116052.2	Q70CQ3
	USP30	NM_001301175.2		c.-10-3949_-10-3947delCGCinsTTG		intron	N/A	NP_001288104.1	B3KUS5
	USP30-AS1	NR_038996.1		n.284_286delGCGinsCAA		non_coding_transcript_exon	Exon 2 of 2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USP30	ENST00000257548.10	TSL:1 MANE Select	c.55_57delCGCinsTTG	p.Arg19Leu	missense	N/A	ENSP00000257548.5	Q70CQ3
	USP30	ENST00000928066.1		c.55_57delCGCinsTTG	p.Arg19Leu	missense	N/A	ENSP00000598125.1
	USP30	ENST00000962121.1		c.55_57delCGCinsTTG	p.Arg19Leu	missense	N/A	ENSP00000632180.1

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.1

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: chr12-109490538;