chr18-45948496-C-A

Variant names:

• chr18-45948496-C-A
• rs202014798
• NM_020964.3:c.1571+7G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_020964.3(EPG5):​c.1571+7G>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,458,134 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: EPG5 NM_020964.3 splice_region, intron
• Scores: Splicing: ADA: 0.0001313
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.536
• 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: ClinGen, G2P, Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

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

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.3).

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.1571+7G>T		splice_region intron	N/A	NP_066015.2	Q9HCE0-1
	EPG5	NM_001410859.1		c.1571+7G>T		splice_region intron	N/A	NP_001397788.1	A0A8Q3SIU6
	EPG5	NM_001410858.1		c.1571+7G>T		splice_region intron	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.1571+7G>T		splice_region intron	N/A	ENSP00000282041.4	Q9HCE0-1
	EPG5	ENST00000587884.2	TSL:1	n.1571+7G>T		splice_region intron	N/A	ENSP00000466990.2	K7ENK5
	EPG5	ENST00000587974.1	TSL:1	n.1606+7G>T		splice_region intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 152196 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1458134 Hom.: 0 Cov.: 29 AF XY: 0.00000138 AC XY: 1 AN XY: 725748

African (AFR) AF: 0.00 AC: 0 AN: 33388

American (AMR) AF: 0.00 AC: 0 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26096

East Asian (EAS) AF: 0.00 AC: 0 AN: 39674

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86180

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53288

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1108754

Other (OTH) AF: 0.00 AC: 0 AN: 60282

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 152314 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74484

African (AFR) AF: 0.00 AC: 0 AN: 41570

American (AMR) AF: 0.00 AC: 0 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68024

Other (OTH) AF: 0.00 AC: 0 AN: 2114

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.30
CADD	Benign	10
DANN	Benign	0.79
PhyloP100		0.54

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00013
dbscSNV1_RF	Benign	0.0
SpliceAI score (max)		0.010		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: rs202014798; hg19: chr18-43528462;