NM_020964.3:c.6622-10_6622-7delTTTT

Variant names:

• chr18-45865765-CAAAA-C
• rs11333207
• NM_020964.3:c.6622-10_6622-7delTTTT

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_020964.3(EPG5):​c.6622-10_6622-7delTTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000214 in 1,407,098 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 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 0.000039 (0 hom., cov: 25)
  • Exomes 𝑓: 0.00023 (0 hom.)
• Consequence: EPG5 NM_020964.3 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.635

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EPG5	NM_020964.3	c.6622-10_6622-7delTTTT		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.6622-10_6622-7delTTTT		splice_region_variant, intron_variant	Intron 38 of 43	1	NM_020964.3	ENSP00000282041.4

Frequencies

GnomAD3 genomes AF: 0.0000390 AC: 4 AN: 102552 Hom.: 0 Cov.: 25

Gnomad AFR AF: 0.0000795

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: 0.000160

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000210

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000228 AC: 297 AN: 1304536 Hom.: 0 AF XY: 0.000243 AC XY: 157 AN XY: 645178

Gnomad4 AFR exome AF: 0.000354

Gnomad4 AMR exome AF: 0.000847

Gnomad4 ASJ exome AF: 0.000535

Gnomad4 EAS exome AF: 0.000321

Gnomad4 SAS exome AF: 0.000443

Gnomad4 FIN exome AF: 0.000642

Gnomad4 NFE exome AF: 0.000163

Gnomad4 OTH exome AF: 0.000258

GnomAD4 genome AF: 0.0000390 AC: 4 AN: 102562 Hom.: 0 Cov.: 25 AF XY: 0.0000406 AC XY: 2 AN XY: 49284

Gnomad4 AFR AF: 0.0000794

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000160

Gnomad4 NFE AF: 0.0000210

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs11333207; hg19: chr18-43445730;