chr18-45838863-G-A
Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2
The NM_213602.3(SIGLEC15):c.642G>A(p.Pro214=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.01 in 1,582,544 control chromosomes in the GnomAD database, including 113 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.0070 ( 7 hom., cov: 33)
Exomes 𝑓: 0.010 ( 106 hom. )
Consequence
SIGLEC15
NM_213602.3 synonymous
NM_213602.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.80
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -11 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.81).
BP6
?
Variant 18-45838863-G-A is Benign according to our data. Variant chr18-45838863-G-A is described in ClinVar as [Benign]. Clinvar id is 1879395.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=-1.8 with no splicing effect.
BS2
?
High Homozygotes in GnomAd at 7 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SIGLEC15 | NM_213602.3 | c.642G>A | p.Pro214= | synonymous_variant | 4/6 | ENST00000389474.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SIGLEC15 | ENST00000389474.8 | c.642G>A | p.Pro214= | synonymous_variant | 4/6 | 1 | NM_213602.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00704 AC: 1071AN: 152188Hom.: 7 Cov.: 33
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GnomAD3 exomes AF: 0.00686 AC: 1301AN: 189532Hom.: 11 AF XY: 0.00700 AC XY: 736AN XY: 105180
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GnomAD4 exome AF: 0.0104 AC: 14829AN: 1430242Hom.: 106 Cov.: 30 AF XY: 0.0101 AC XY: 7186AN XY: 709936
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GnomAD4 genome ? AF: 0.00703 AC: 1071AN: 152302Hom.: 7 Cov.: 33 AF XY: 0.00706 AC XY: 526AN XY: 74472
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Nov 01, 2022 | EPG5: BS1, BS2; SIGLEC15: BP4, BP7, BS1, BS2 - |
Computational scores
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at