18-45880111-AAG-CAA

Variant names:

• chr18-45880111-AAG-CAA
• NM_020964.3:c.5629_5631delCTTinsTTG
• EPG5 p.1878

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP7

The NM_020964.3(EPG5):​c.5629_5631delCTTinsTTG​(p.1878) variant causes a synonymous 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. Synonymous variant affecting the same amino acid position (i.e. L1877L) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: EPG5 NM_020964.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.74
• Publications: 0 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: G2P, Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• BP7: Synonymous conserved (PhyloP=2.74 with no splicing effect.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EPG5	NM_020964.3	MANE Select	c.5629_5631delCTTinsTTG	p.1878	synonymous	N/A	NP_066015.2	Q9HCE0-1
	EPG5	NM_001410859.1		c.5629_5631delCTTinsTTG	p.1878	synonymous	N/A	NP_001397788.1	A0A8Q3SIU6
	EPG5	NM_001410858.1		c.5629_5631delCTTinsTTG	p.1878	synonymous	N/A	NP_001397787.1	A0A8Q3SIJ2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EPG5	ENST00000282041.11	TSL:1 MANE Select	c.5629_5631delCTTinsTTG	p.1878	synonymous	N/A	ENSP00000282041.4	Q9HCE0-1
	EPG5	ENST00000587884.2	TSL:1	n.*1369_*1371delCTTinsTTG		non_coding_transcript_exon	Exon 33 of 45	ENSP00000466990.2	K7ENK5
	EPG5	ENST00000590884.6	TSL:1	n.*224_*226delCTTinsTTG		non_coding_transcript_exon	Exon 32 of 42	ENSP00000466403.2	K7EM87

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		2.7

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: chr18-43460076;