rs72918350

Variant names:

• chr18-45916543-G-A
• rs72918350
• NM_020964.3:c.3279C>T
• EPG5 p.Ser1093Ser

Your query was ambiguous. Multiple possible variants found:

• chr18-45916543-G-A
• chr18-45916543-G-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_020964.3(EPG5):​c.3279C>T​(p.Ser1093Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0121 in 1,610,766 control chromosomes in the GnomAD database, including 147 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0088 (13 hom., cov: 32)
  • Exomes 𝑓: 0.012 (134 hom.)
• Consequence: EPG5 NM_020964.3 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.424
• Publications: 1 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: G2P, Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP6: Variant 18-45916543-G-A is Benign according to our data. Variant chr18-45916543-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 466246.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.424 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00877 (1335/152242) while in subpopulation NFE AF = 0.014 (952/68000). AF 95% confidence interval is 0.0133. There are 13 homozygotes in GnomAd4. There are 650 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 13 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EPG5	NM_020964.3	MANE Select	c.3279C>T	p.Ser1093Ser	synonymous	Exon 18 of 44	NP_066015.2	Q9HCE0-1
	EPG5	NM_001410859.1		c.3279C>T	p.Ser1093Ser	synonymous	Exon 18 of 44	NP_001397788.1	A0A8Q3SIU6
	EPG5	NM_001410858.1		c.3279C>T	p.Ser1093Ser	synonymous	Exon 18 of 44	NP_001397787.1	A0A8Q3SIJ2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EPG5	ENST00000282041.11	TSL:1 MANE Select	c.3279C>T	p.Ser1093Ser	synonymous	Exon 18 of 44	ENSP00000282041.4	Q9HCE0-1
	EPG5	ENST00000587884.2	TSL:1	n.3279C>T		non_coding_transcript_exon	Exon 18 of 45	ENSP00000466990.2	K7ENK5
	EPG5	ENST00000587974.1	TSL:1	n.3314C>T		non_coding_transcript_exon	Exon 18 of 24

Frequencies

GnomAD3 genomes AF: 0.00878 AC: 1336 AN: 152124 Hom.: 14 Cov.: 32

Gnomad AFR AF: 0.00217

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00484

Gnomad ASJ AF: 0.00404

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00311

Gnomad FIN AF: 0.0160

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0140

Gnomad OTH AF: 0.00815

GnomAD2 exomes AF: 0.00954 AC: 2376 AN: 249160 AF XY: 0.00942

Gnomad AFR exome AF: 0.00265

Gnomad AMR exome AF: 0.00592

Gnomad ASJ exome AF: 0.00487

Gnomad EAS exome AF: 0.0000557

Gnomad FIN exome AF: 0.0155

Gnomad NFE exome AF: 0.0142

Gnomad OTH exome AF: 0.00958

GnomAD4 exome AF: 0.0124 AC: 18099 AN: 1458524 Hom.: 134 Cov.: 31 AF XY: 0.0121 AC XY: 8790 AN XY: 724758

African (AFR) AF: 0.00206 AC: 69 AN: 33420

American (AMR) AF: 0.00575 AC: 257 AN: 44670

Ashkenazi Jewish (ASJ) AF: 0.00613 AC: 160 AN: 26104

East Asian (EAS) AF: 0.0000253 AC: 1 AN: 39566

South Asian (SAS) AF: 0.00306 AC: 264 AN: 86174

European-Finnish (FIN) AF: 0.0143 AC: 766 AN: 53380

Middle Eastern (MID) AF: 0.00556 AC: 32 AN: 5758

European-Non Finnish (NFE) AF: 0.0144 AC: 15925 AN: 1109226

Other (OTH) AF: 0.0104 AC: 625 AN: 60226

GnomAD4 genome AF: 0.00877 AC: 1335 AN: 152242 Hom.: 13 Cov.: 32 AF XY: 0.00873 AC XY: 650 AN XY: 74446

African (AFR) AF: 0.00217 AC: 90 AN: 41558

American (AMR) AF: 0.00484 AC: 74 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00404 AC: 14 AN: 3466

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5186

South Asian (SAS) AF: 0.00332 AC: 16 AN: 4814

European-Finnish (FIN) AF: 0.0160 AC: 170 AN: 10610

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0140 AC: 952 AN: 68000

Other (OTH) AF: 0.00806 AC: 17 AN: 2108

Alfa AF: 0.0118 Hom.: 28

Bravo AF: 0.00822

Asia WGS AF: 0.00231 AC: 9 AN: 3478

EpiCase AF: 0.0140

EpiControl AF: 0.0133

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	EPG5-related disorder (1)
-	-	1	Vici syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	7.9
DANN	Benign	0.86
PhyloP100		-0.42
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.16		Details are displayed if max score is > 0.2

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs72918350;

hg19: chr18-43496508;