NM_024818.6:c.90delC

Variant names:

• chr3-132660626-GC-G
• NM_024818.6:c.90delC

Variant summary

Our verdict is Pathogenic. The variant received 12 ACMG points: 12P and 0B. PVS1 PM2 PP5_Moderate

The NM_024818.6(UBA5):​c.90delC​(p.Ser30ArgfsTer14) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: UBA5 NM_024818.6 frameshift
• Clinical Significance: Pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 0.114
• Publications: 0 publications found

Genes affected

UBA5 (HGNC:23230): (ubiquitin like modifier activating enzyme 5) This gene encodes a member of the E1-like ubiquitin-activating enzyme family. This protein activates ubiquitin-fold modifier 1, a ubiquitin-like post-translational modifier protein, via the formation of a high-energy thioester bond. Alternative splicing results in multiple transcript variants. A pseudogene of this gene has been identified on chromosome 1. [provided by RefSeq, Feb 2016]

NPHP3-ACAD11 (HGNC:48351): (NPHP3-ACAD11 readthrough (NMD candidate)) This locus represents naturally occurring read-through transcription between the neighboring NPHP3 (nephronophthisis 3, adolescent) and ACAD11 (acyl-CoA dehydrogenase family, member 11) genes on chromosome 3. The read-through transcript is a candidate for nonsense-mediated mRNA decay (NMD), and is thus unlikely to produce a protein product. [provided by RefSeq, Feb 2011]

ACMG classification

Our verdict: Pathogenic. The variant received 12 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 39 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 3-132660626-GC-G is Pathogenic according to our data. Variant chr3-132660626-GC-G is described in ClinVar as Pathogenic. ClinVar VariationId is 1971012.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024818.6. 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
	UBA5	NM_024818.6	MANE Select	c.90delC	p.Ser30ArgfsTer14	frameshift	Exon 1 of 12	NP_079094.1	Q9GZZ9-1
	UBA5	NM_001320210.2		c.-429delC		5_prime_UTR	Exon 1 of 12	NP_001307139.1	Q9GZZ9-2
	UBA5	NM_001321238.2		c.-395delC		5_prime_UTR	Exon 1 of 10	NP_001308167.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBA5	ENST00000356232.10	TSL:1 MANE Select	c.90delC	p.Ser30ArgfsTer14	frameshift	Exon 1 of 12	ENSP00000348565.4	Q9GZZ9-1
	UBA5	ENST00000494238.6	TSL:1	c.-429delC		5_prime_UTR	Exon 1 of 12	ENSP00000418807.2	Q9GZZ9-2
	NPHP3-ACAD11	ENST00000632629.1	TSL:2	c.636-15731delG		intron	N/A	ENSP00000488520.1	A0A0J9YXS1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions as Germline

Significance: Pathogenic

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.11
Mutation Taster		=4/196	disease causing (fs/PTC)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr3-132379470;