rs1408072461

Variant names:

• chr18-45837788-G-A
• rs1408072461
• NM_213602.3:c.388G>A

Your query was ambiguous. Multiple possible variants found:

• chr18-45837788-G-A
• chr18-45837788-G-C

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_213602.3(SIGLEC15):​c.388G>A​(p.Glu130Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000584 in 1,370,754 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. E130Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000058 (0 hom.)
• Consequence: SIGLEC15 NM_213602.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.36
• 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: Likely_benign. The variant received -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.32666987).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SIGLEC15	NM_213602.3	c.388G>A	p.Glu130Lys	missense_variant	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.388G>A	p.Glu130Lys	missense_variant	Exon 3 of 6	1	NM_213602.3	ENSP00000374125.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00 AC: 0 AN: 120778 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000584 AC: 8 AN: 1370754 Hom.: 0 Cov.: 32 AF XY: 0.00000295 AC XY: 2 AN XY: 677734

African (AFR) AF: 0.00 AC: 0 AN: 28218

American (AMR) AF: 0.00 AC: 0 AN: 36208

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24332

East Asian (EAS) AF: 0.000246 AC: 8 AN: 32584

South Asian (SAS) AF: 0.00 AC: 0 AN: 78384

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33710

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4382

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1075924

Other (OTH) AF: 0.00 AC: 0 AN: 57012

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.44
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0019	T
Eigen	Uncertain	0.25
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.66	T
M_CAP	Benign	0.085	D
MetaRNN	Benign	0.33	T
MetaSVM	Benign	-0.75	T
MutationAssessor	Benign	0.90	L
PhyloP100		5.4
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-0.51	N
REVEL	Benign	0.18
Sift	Benign	0.47	T
Sift4G	Benign	0.11	T
Polyphen		0.82	P
Vest4		0.29
MutPred		0.57		Gain of MoRF binding (P = 0.0021);
MVP		0.70
MPC		0.89
ClinPred		0.78	D
GERP RS		3.7
PromoterAI		0.047	Neutral
Varity_R		0.24
gMVP		0.46
Mutation Taster		=81/19	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1408072461; hg19: chr18-43417753;