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GeneBe

18-45838863-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

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.80
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]
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
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.81).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
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
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-1.8 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 7 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SIGLEC15NM_213602.3 linkuse as main transcriptc.642G>A p.Pro214= synonymous_variant 4/6 ENST00000389474.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SIGLEC15ENST00000389474.8 linkuse as main transcriptc.642G>A p.Pro214= synonymous_variant 4/61 NM_213602.3 P1Q6ZMC9-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00704
AC:
1071
AN:
152188
Hom.:
7
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00224
Gnomad AMI
AF:
0.0175
Gnomad AMR
AF:
0.00517
Gnomad ASJ
AF:
0.0107
Gnomad EAS
AF:
0.000193
Gnomad SAS
AF:
0.00104
Gnomad FIN
AF:
0.00499
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0114
Gnomad OTH
AF:
0.00525
GnomAD3 exomes
AF:
0.00686
AC:
1301
AN:
189532
Hom.:
11
AF XY:
0.00700
AC XY:
736
AN XY:
105180
show subpopulations
Gnomad AFR exome
AF:
0.00172
Gnomad AMR exome
AF:
0.00547
Gnomad ASJ exome
AF:
0.00935
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00167
Gnomad FIN exome
AF:
0.00316
Gnomad NFE exome
AF:
0.0109
Gnomad OTH exome
AF:
0.0116
GnomAD4 exome
AF:
0.0104
AC:
14829
AN:
1430242
Hom.:
106
Cov.:
30
AF XY:
0.0101
AC XY:
7186
AN XY:
709936
show subpopulations
Gnomad4 AFR exome
AF:
0.00125
Gnomad4 AMR exome
AF:
0.00554
Gnomad4 ASJ exome
AF:
0.00946
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00151
Gnomad4 FIN exome
AF:
0.00466
Gnomad4 NFE exome
AF:
0.0123
Gnomad4 OTH exome
AF:
0.00825
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00703
AC:
1071
AN:
152302
Hom.:
7
Cov.:
33
AF XY:
0.00706
AC XY:
526
AN XY:
74472
show subpopulations
Gnomad4 AFR
AF:
0.00224
Gnomad4 AMR
AF:
0.00516
Gnomad4 ASJ
AF:
0.0107
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.00104
Gnomad4 FIN
AF:
0.00499
Gnomad4 NFE
AF:
0.0114
Gnomad4 OTH
AF:
0.00520
Alfa
AF:
0.00627
Hom.:
4
Bravo
AF:
0.00646

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 submitterclinical testingCeGaT Center for Human Genetics TuebingenNov 01, 2022EPG5: BS1, BS2; SIGLEC15: BP4, BP7, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.81
Cadd
Benign
1.1
Dann
Benign
0.80

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs201159400; hg19: chr18-43418828; API