NM_020964.3:c.2257+10C>T

Variant names:

• chr18-45934799-G-A
• rs202068698
• NM_020964.3:c.2257+10C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_020964.3(EPG5):​c.2257+10C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000475 in 1,595,892 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0026 (5 hom., cov: 32)
  • Exomes 𝑓: 0.00025 (0 hom.)
• Consequence: EPG5 NM_020964.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.789
• Publications: 0 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: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 18-45934799-G-A is Benign according to our data. Variant chr18-45934799-G-A is described in ClinVar as Benign. ClinVar VariationId is 466242.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0026 (396/152268) while in subpopulation AFR AF = 0.00919 (382/41552). AF 95% confidence interval is 0.00843. There are 5 homozygotes in GnomAd4. There are 188 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 5 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020964.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EPG5	NM_020964.3	MANE Select	c.2257+10C>T		intron	N/A	NP_066015.2
	EPG5	NM_001410859.1		c.2257+10C>T		intron	N/A	NP_001397788.1
	EPG5	NM_001410858.1		c.2257+10C>T		intron	N/A	NP_001397787.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EPG5	ENST00000282041.11	TSL:1 MANE Select	c.2257+10C>T		intron	N/A	ENSP00000282041.4
	EPG5	ENST00000587884.2	TSL:1	n.2257+10C>T		intron	N/A	ENSP00000466990.2
	EPG5	ENST00000587974.1	TSL:1	n.2292+10C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00260 AC: 396 AN: 152150 Hom.: 5 Cov.: 32

Gnomad AFR AF: 0.00922

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000655

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: 0.0000441

Gnomad OTH AF: 0.000480

GnomAD2 exomes AF: 0.000814 AC: 190 AN: 233310 AF XY: 0.000607

Gnomad AFR exome AF: 0.0117

Gnomad AMR exome AF: 0.000203

Gnomad ASJ exome AF: 0.000113

Gnomad EAS exome AF: 0.0000580

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000278

Gnomad OTH exome AF: 0.000178

GnomAD4 exome AF: 0.000251 AC: 362 AN: 1443624 Hom.: 0 Cov.: 30 AF XY: 0.000215 AC XY: 154 AN XY: 717388

African (AFR) AF: 0.00966 AC: 315 AN: 32592

American (AMR) AF: 0.000229 AC: 9 AN: 39306

Ashkenazi Jewish (ASJ) AF: 0.0000400 AC: 1 AN: 25014

East Asian (EAS) AF: 0.0000253 AC: 1 AN: 39522

South Asian (SAS) AF: 0.0000360 AC: 3 AN: 83312

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53214

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5646

European-Non Finnish (NFE) AF: 0.0000109 AC: 12 AN: 1105440

Other (OTH) AF: 0.000352 AC: 21 AN: 59578

GnomAD4 genome AF: 0.00260 AC: 396 AN: 152268 Hom.: 5 Cov.: 32 AF XY: 0.00253 AC XY: 188 AN XY: 74448

African (AFR) AF: 0.00919 AC: 382 AN: 41552

American (AMR) AF: 0.000654 AC: 10 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68020

Other (OTH) AF: 0.000475 AC: 1 AN: 2104

Alfa AF: 0.00236 Hom.: 2

Bravo AF: 0.00309

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Vici syndrome Benign:1

Jan 20, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.068
DANN	Benign	0.56
PhyloP100		-0.79
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs202068698; hg19: chr18-43514765;