rs1555658766

Variant names:

• chr18-45852533-T-C
• rs1555658766
• NM_020964.3:c.7674A>G

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_020964.3(EPG5):​c.7674A>G​(p.Lys2558Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,884 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: EPG5 NM_020964.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.418
• 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: Likely_benign. The variant received -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP6: Variant 18-45852533-T-C is Benign according to our data. Variant chr18-45852533-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 534618.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.418 with no splicing effect.

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.7674A>G	p.Lys2558Lys	synonymous	Exon 44 of 44	NP_066015.2
	EPG5	NM_001410859.1		c.7671A>G	p.Lys2557Lys	synonymous	Exon 44 of 44	NP_001397788.1
	EPG5	NM_001410858.1		c.7557+3040A>G		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.7674A>G	p.Lys2558Lys	synonymous	Exon 44 of 44	ENSP00000282041.4
	EPG5	ENST00000587884.2	TSL:1	n.*3414A>G		non_coding_transcript_exon	Exon 45 of 45	ENSP00000466990.2
	EPG5	ENST00000590884.6	TSL:1	n.*1986A>G		non_coding_transcript_exon	Exon 42 of 42	ENSP00000466403.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461884 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727240

African (AFR) AF: 0.0000597 AC: 2 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112006

Other (OTH) AF: 0.0000166 AC: 1 AN: 60394

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Vici syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	5.5
DANN	Benign	0.59
PhyloP100		0.42

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: rs1555658766; hg19: chr18-43432498;