NM_213602.3:c.163G>T

Variant names:

• chr18-45837563-G-T
• rs1355483990
• NM_213602.3:c.163G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_213602.3(SIGLEC15):​c.163G>T​(p.Glu55*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000733 in 1,364,122 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.3e-7 (0 hom.)
• Consequence: SIGLEC15 NM_213602.3 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.23
• Publications: 0 publications found

Genes affected

SIGLEC15 (HGNC:27596): (sialic acid binding Ig like lectin 15) Predicted to be involved in regulation of actin cytoskeleton organization; regulation of bone resorption; and regulation of osteoclast development. Predicted to be integral component of membrane. Predicted to be part of protein-containing complex. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SIGLEC15	NM_213602.3	c.163G>T	p.Glu55*	stop_gained	Exon 3 of 6	ENST00000389474.8	NP_998767.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SIGLEC15	ENST00000389474.8	c.163G>T	p.Glu55*	stop_gained	Exon 3 of 6	1	NM_213602.3	ENSP00000374125.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.33e-7 AC: 1 AN: 1364122 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 673088

African (AFR) AF: 0.00 AC: 0 AN: 28370

American (AMR) AF: 0.0000293 AC: 1 AN: 34162

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24396

East Asian (EAS) AF: 0.00 AC: 0 AN: 33396

South Asian (SAS) AF: 0.00 AC: 0 AN: 77860

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33372

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4072

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1071576

Other (OTH) AF: 0.00 AC: 0 AN: 56918

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.37	D
BayesDel_noAF	Pathogenic	0.29
CADD	Pathogenic	36
DANN	Uncertain	0.99
Eigen	Benign	0.18
Eigen_PC	Benign	-0.097
FATHMM_MKL	Benign	0.68	D
PhyloP100		2.2
Vest4		0.11
GERP RS		2.1
PromoterAI		0.021	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs1355483990; hg19: chr18-43417528;