chr18-45838827-G-A
Position:
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7
The NM_213602.3(SIGLEC15):c.606G>A(p.Pro202=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000403 in 1,563,838 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.000039 ( 1 hom., cov: 33)
Exomes 𝑓: 0.000040 ( 0 hom. )
Consequence
SIGLEC15
NM_213602.3 synonymous
NM_213602.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.81
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -5 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.74).
BP6
Variant 18-45838827-G-A is Benign according to our data. Variant chr18-45838827-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1879394.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-1.81 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SIGLEC15 | NM_213602.3 | c.606G>A | p.Pro202= | synonymous_variant | 4/6 | ENST00000389474.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SIGLEC15 | ENST00000389474.8 | c.606G>A | p.Pro202= | synonymous_variant | 4/6 | 1 | NM_213602.3 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000394 AC: 6AN: 152114Hom.: 1 Cov.: 33
GnomAD3 genomes
AF:
AC:
6
AN:
152114
Hom.:
Cov.:
33
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.0000485 AC: 8AN: 165110Hom.: 0 AF XY: 0.0000766 AC XY: 7AN XY: 91396
GnomAD3 exomes
AF:
AC:
8
AN:
165110
Hom.:
AF XY:
AC XY:
7
AN XY:
91396
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0000404 AC: 57AN: 1411724Hom.: 0 Cov.: 30 AF XY: 0.0000615 AC XY: 43AN XY: 699350
GnomAD4 exome
AF:
AC:
57
AN:
1411724
Hom.:
Cov.:
30
AF XY:
AC XY:
43
AN XY:
699350
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome AF: 0.0000394 AC: 6AN: 152114Hom.: 1 Cov.: 33 AF XY: 0.0000807 AC XY: 6AN XY: 74304
GnomAD4 genome
AF:
AC:
6
AN:
152114
Hom.:
Cov.:
33
AF XY:
AC XY:
6
AN XY:
74304
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Bravo
AF:
ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Dec 01, 2022 | SIGLEC15: BP4, BP7 - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at