18-45865765-CAAAAAAA-CAAAAAAAAAAAAAAAAAAAA

Variant names:

• chr18-45865765-C-CAAAAAAAAAAAAA
• rs11333207
• NM_020964.3:c.6622-19_6622-7dupTTTTTTTTTTTTT

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP6_Moderate

The NM_020964.3(EPG5):​c.6622-19_6622-7dupTTTTTTTTTTTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000475 in 1,411,738 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00020 (0 hom., cov: 25)
  • Exomes 𝑓: 0.000035 (0 hom.)
• Consequence: EPG5 NM_020964.3 splice_region, intron
• Clinical Significance: Likely benign criteria provided, single submitter 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 18-45865765-C-CAAAAAAAAAAAAA is Benign according to our data. Variant chr18-45865765-C-CAAAAAAAAAAAAA is described in ClinVar as [Likely_benign]. Clinvar id is 2077447.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EPG5	NM_020964.3	c.6622-19_6622-7dupTTTTTTTTTTTTT		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_6622-6insTTTTTTTTTTTTT		splice_region_variant, intron_variant	Intron 38 of 43	1	NM_020964.3	ENSP00000282041.4

Frequencies

GnomAD3 genomes AF: 0.000205 AC: 21 AN: 102544 Hom.: 0 Cov.: 25

Gnomad AFR AF: 0.000756

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000176

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: 0.0000351 AC: 46 AN: 1309184 Hom.: 0 Cov.: 0 AF XY: 0.0000340 AC XY: 22 AN XY: 647488

Gnomad4 AFR exome AF: 0.000883

Gnomad4 AMR exome AF: 0.0000325

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000147

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000146

Gnomad4 OTH exome AF: 0.0000735

GnomAD4 genome AF: 0.000205 AC: 21 AN: 102554 Hom.: 0 Cov.: 25 AF XY: 0.000223 AC XY: 11 AN XY: 49278

Gnomad4 AFR AF: 0.000754

Gnomad4 AMR AF: 0.000176

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

Bravo AF: 0.00000378

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Vici syndrome Benign:1

Nov 27, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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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;