chr18-45865765-CAAAAAAA-C

Variant names:

• chr18-45865765-CAAAAAAA-C
• rs11333207
• NM_020964.3:c.6622-13_6622-7delTTTTTTT

Variant summary

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

The NM_020964.3(EPG5):​c.6622-13_6622-7delTTTTTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000425 in 1,411,854 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000039 (0 hom., cov: 25)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: EPG5 NM_020964.3 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.635
• Publications: 3 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: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EPG5	NM_020964.3	c.6622-13_6622-7delTTTTTTT		splice_region_variant, intron_variant	Intron 38 of 43	ENST00000282041.11	NP_066015.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EPG5	ENST00000282041.11	c.6622-13_6622-7delTTTTTTT		splice_region_variant, intron_variant	Intron 38 of 43	1	NM_020964.3	ENSP00000282041.4

Frequencies

GnomAD3 genomes AF: 0.0000390 AC: 4 AN: 102560 Hom.: 0 Cov.: 25

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000352

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: 0.00000153 AC: 2 AN: 1309294 Hom.: 0 AF XY: 0.00000309 AC XY: 2 AN XY: 647538

African (AFR) AF: 0.00 AC: 0 AN: 28372

American (AMR) AF: 0.00 AC: 0 AN: 30794

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20628

East Asian (EAS) AF: 0.00 AC: 0 AN: 37546

South Asian (SAS) AF: 0.00 AC: 0 AN: 68130

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37564

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4242

European-Non Finnish (NFE) AF: 0.00000195 AC: 2 AN: 1027586

Other (OTH) AF: 0.00 AC: 0 AN: 54432

GnomAD4 genome AF: 0.0000390 AC: 4 AN: 102560 Hom.: 0 Cov.: 25 AF XY: 0.0000609 AC XY: 3 AN XY: 49252

African (AFR) AF: 0.00 AC: 0 AN: 25154

American (AMR) AF: 0.000352 AC: 4 AN: 11364

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2386

East Asian (EAS) AF: 0.00 AC: 0 AN: 3992

South Asian (SAS) AF: 0.00 AC: 0 AN: 3644

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6252

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 164

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 47580

Other (OTH) AF: 0.00 AC: 0 AN: 1434

Alfa AF: 0.00 Hom.: 20

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.64

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs11333207; hg19: chr18-43445730;