chr18-45800871-A-T

Variant names:

• chr18-45800871-A-T
• rs559774
• NM_001410858.1:c.7577T>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001410858.1(EPG5):​c.7577T>A​(p.Phe2526Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 4/4 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. F2526S) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: EPG5 NM_001410858.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.744
• Publications: 3 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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EPG5	NM_001410858.1	c.7577T>A	p.Phe2526Tyr	missense_variant	Exon 44 of 44		NP_001397787.1
EPG5	XM_047437703.1	c.7604T>A	p.Phe2535Tyr	missense_variant	Exon 44 of 44		XP_047293659.1
EPG5	XM_047437704.1	c.7601T>A	p.Phe2534Tyr	missense_variant	Exon 44 of 44		XP_047293660.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EPG5	ENST00000696483.1	c.7577T>A	p.Phe2526Tyr	missense_variant	Exon 44 of 44			ENSP00000512657.1
EPG5	ENST00000696484.1	c.7462T>A	p.Leu2488Ile	missense_variant	Exon 43 of 43			ENSP00000512658.1
EPG5	ENST00000696481.1	n.4094T>A		non_coding_transcript_exon_variant	Exon 16 of 16
EPG5	ENST00000696491.1	n.160T>A		non_coding_transcript_exon_variant	Exon 2 of 2

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	8.3
DANN	Benign	0.47
PhyloP100		0.74

Splicing

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

Other links and lift over

dbSNP: rs559774; hg19: chr18-43380836;