NM_020964.3:c.5792delT

Variant names:

• chr18-45879089-CA-C
• rs1135402727
• NM_020964.3:c.5792delT

Variant summary

Our verdict is Pathogenic. The variant received 10 ACMG points: 10P and 0B. PVS1 PM2

The NM_020964.3(EPG5):​c.5792delT​(p.Leu1931TrpfsTer5) variant causes a frameshift change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as no classification for the single variant (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: EPG5 NM_020964.3 frameshift
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.51
• Publications: 1 publications found

Genes affected

EPG5 (HGNC:29331): (ectopic P-granules 5 autophagy tethering factor) This gene encodes a large coiled coil domain-containing protein that functions in autophagy during starvation conditions. Mutations in this gene cause Vici syndrome. [provided by RefSeq, Aug 2015]

EPG5 Gene-Disease associations (from GenCC):

• Vici syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet, G2P

ACMG classification

Our verdict: Pathogenic. The variant received 10 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020964.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EPG5	NM_020964.3	MANE Select	c.5792delT	p.Leu1931TrpfsTer5	frameshift	Exon 33 of 44	NP_066015.2
	EPG5	NM_001410859.1		c.5792delT	p.Leu1931TrpfsTer5	frameshift	Exon 33 of 44	NP_001397788.1
	EPG5	NM_001410858.1		c.5792delT	p.Leu1931TrpfsTer5	frameshift	Exon 33 of 44	NP_001397787.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EPG5	ENST00000282041.11	TSL:1 MANE Select	c.5792delT	p.Leu1931TrpfsTer5	frameshift	Exon 33 of 44	ENSP00000282041.4
	EPG5	ENST00000587884.2	TSL:1	n.*1532delT		non_coding_transcript_exon	Exon 34 of 45	ENSP00000466990.2
	EPG5	ENST00000590884.6	TSL:1	n.*387delT		non_coding_transcript_exon	Exon 33 of 42	ENSP00000466403.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		4.5
Mutation Taster		=5/195	disease causing (fs/PTC)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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

dbSNP: rs1135402727; hg19: chr18-43459054;