18-45865765-CAAAAAAA-CAAAAAAAAAAA

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP6

The NM_020964.3(EPG5):​c.6622-10_6622-7dupTTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000368 in 1,411,788 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.00023 (0 hom., cov: 25)
  • Exomes 𝑓: 0.000021 (0 hom.)
• Consequence: EPG5 NM_020964.3 splice_region, intron
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.327

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 18-45865765-C-CAAAA is Benign according to our data. Variant chr18-45865765-C-CAAAA is described in ClinVar as [Likely_benign]. Clinvar id is 3357211.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EPG5	NM_020964.3	c.6622-10_6622-7dupTTTT		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.6622-7_6622-6insTTTT		splice_region_variant, intron_variant	Intron 38 of 43	1	NM_020964.3	ENSP00000282041.4

Frequencies

GnomAD3 genomes AF: 0.000234 AC: 24 AN: 102556 Hom.: 0 Cov.: 25

Gnomad AFR AF: 0.000954

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: 0.0000214 AC: 28 AN: 1309222 Hom.: 0 Cov.: 0 AF XY: 0.0000247 AC XY: 16 AN XY: 647504

Gnomad4 AFR exome AF: 0.000564

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.0000485

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000147

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000876

Gnomad4 OTH exome AF: 0.0000184

GnomAD4 genome AF: 0.000234 AC: 24 AN: 102566 Hom.: 0 Cov.: 25 AF XY: 0.000284 AC XY: 14 AN XY: 49282

Gnomad4 AFR AF: 0.000952

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

EPG5-related disorder Benign:1

Aug 28, 2019

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Splicing

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;