NM_020964.3:c.6622-8_6622-7dupTT

Variant names:

• chr18-45865765-C-CAA
• rs11333207
• NM_020964.3:c.6622-8_6622-7dupTT

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BS1

The NM_020964.3(EPG5):​c.6622-8_6622-7dupTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00182 in 1,407,766 control chromosomes in the GnomAD database, including 1 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00019 (0 hom., cov: 25)
  • Exomes 𝑓: 0.0019 (1 hom.)
• Consequence: EPG5 NM_020964.3 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• 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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BS1: Variant frequency is greater than expected in population sas. gnomad4_exome allele frequency = 0.00195 (2543/1305202) while in subpopulation SAS AF= 0.00219 (149/67922). AF 95% confidence interval is 0.00191. There are 1 homozygotes in gnomad4_exome. There are 1280 alleles in male gnomad4_exome subpopulation. Median coverage is 0. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EPG5	NM_020964.3	c.6622-8_6622-7dupTT		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_6622-6insTT		splice_region_variant, intron_variant	Intron 38 of 43	1	NM_020964.3	ENSP00000282041.4

Frequencies

GnomAD3 genomes AF: 0.000185 AC: 19 AN: 102554 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: 0.000960

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000189

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00195 AC: 2543 AN: 1305202 Hom.: 1 Cov.: 0 AF XY: 0.00198 AC XY: 1280 AN XY: 645520

Gnomad4 AFR exome AF: 0.00173

Gnomad4 AMR exome AF: 0.00218

Gnomad4 ASJ exome AF: 0.00141

Gnomad4 EAS exome AF: 0.00152

Gnomad4 SAS exome AF: 0.00219

Gnomad4 FIN exome AF: 0.00278

Gnomad4 NFE exome AF: 0.00194

Gnomad4 OTH exome AF: 0.00177

GnomAD4 genome AF: 0.000185 AC: 19 AN: 102564 Hom.: 0 Cov.: 25 AF XY: 0.000223 AC XY: 11 AN XY: 49282

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.000352

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000960

Gnomad4 NFE AF: 0.000189

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

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;