Genetic Variant NM_213602.3:c.388G>A (chr18-45837788-G-A) – ACMG Classification: Likely_benign (-1 pts)

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.36

Publications

0 publications found

Variant links:

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]

SIGLEC15 links:

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

EPG5 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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 link	c.388G>A	p.Glu130Lys	missense_variant	Exon 3 of 6	ENST00000389474.8	NP_998767.1	Q6ZMC9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SIGLEC15	ENST00000389474.8 link	c.388G>A	p.Glu130Lys	missense_variant	Exon 3 of 6	1	NM_213602.3	ENSP00000374125.2		Q6ZMC9-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

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:

AN:

1370754

Hom.:

Cov.:

AF XY:

0.00000295

AC XY:

AN XY:

677734

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

28218

American (AMR)

AF:

0.00

AC:

AN:

36208

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24332

East Asian (EAS)

AF:

0.000246

AC:

AN:

32584

South Asian (SAS)

AF:

0.00

AC:

AN:

78384

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33710

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4382

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1075924

Other (OTH)

AF:

0.00

AC:

AN:

57012

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

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

BayesDel_noAF

Benign

-0.40

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0019

Eigen

Uncertain

0.25

Eigen_PC

Uncertain

0.29

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.66

M_CAP

Benign

0.085

MetaRNN

Benign

0.33

MetaSVM

Benign

-0.75

MutationAssessor

Benign

0.90

PhyloP100

5.4

PrimateAI

Pathogenic

0.85

PROVEAN

Benign

-0.51

REVEL

Benign

0.18

Sift

Benign

0.47

Sift4G

Benign

0.11

Polyphen

0.82

Vest4

0.29

MutPred

0.57

Gain of MoRF binding (P = 0.0021);

MVP

0.70

MPC

0.89

ClinPred

0.78

GERP RS

3.7

PromoterAI

0.047

Neutral

(source)

Varity_R

0.24

gMVP

0.46

Mutation Taster

=81/19

polymorphism

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

NM_213602.3:c.388G>A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over