19-51452586-A-C
Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2
The NM_014442.3(SIGLEC8):c.1293T>G(p.Pro431=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00238 in 1,571,174 control chromosomes in the GnomAD database, including 69 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.013 ( 31 hom., cov: 31)
Exomes 𝑓: 0.0013 ( 38 hom. )
Consequence
SIGLEC8
NM_014442.3 synonymous
NM_014442.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -3.43
Genes affected
SIGLEC8 (HGNC:10877): (sialic acid binding Ig like lectin 8) Sialic acid-binding immunoglobulin (Ig)-like lectins, or SIGLECs (e.g., CD33 (MIM 159590)), are a family of type 1 transmembrane proteins each having a unique expression pattern, mostly in hemopoietic cells. SIGLEC8 is a member of the CD33-like subgroup of SIGLECs, which are localized to 19q13.3-q13.4 and have 2 conserved cytoplasmic tyrosine-based motifs: an immunoreceptor tyrosine-based inhibitory motif, or ITIM (see MIM 604964), and a motif homologous to one identified in signaling lymphocyte activation molecule (SLAM; MIM 603492) that mediates an association with SLAM-associated protein (SAP; MIM 300490) (summarized by Foussias et al., 2000 [PubMed 11095983]).[supplied by OMIM, May 2010]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -15 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-1.04).
BP6
?
Variant 19-51452586-A-C is Benign according to our data. Variant chr19-51452586-A-C is described in ClinVar as [Benign]. Clinvar id is 769047.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=-3.43 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0129 (1955/151876) while in subpopulation AFR AF= 0.0443 (1835/41400). AF 95% confidence interval is 0.0426. There are 31 homozygotes in gnomad4. There are 928 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd at 31 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SIGLEC8 | NM_014442.3 | c.1293T>G | p.Pro431= | synonymous_variant | 7/7 | ENST00000321424.7 | |
SIGLEC8 | NM_001363548.1 | c.1014T>G | p.Pro338= | synonymous_variant | 6/6 | ||
SIGLEC8 | XM_011526734.3 | c.1260T>G | p.Pro420= | synonymous_variant | 7/7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SIGLEC8 | ENST00000321424.7 | c.1293T>G | p.Pro431= | synonymous_variant | 7/7 | 1 | NM_014442.3 | P1 | |
SIGLEC8 | ENST00000340550.5 | c.1014T>G | p.Pro338= | synonymous_variant | 6/6 | 1 | |||
SIGLEC8 | ENST00000430817.5 | c.966T>G | p.Pro322= | synonymous_variant | 5/6 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0129 AC: 1955AN: 151758Hom.: 31 Cov.: 31
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GnomAD3 exomes AF: 0.00362 AC: 827AN: 228606Hom.: 23 AF XY: 0.00252 AC XY: 312AN XY: 123818
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GnomAD4 exome AF: 0.00125 AC: 1777AN: 1419298Hom.: 38 Cov.: 32 AF XY: 0.00105 AC XY: 739AN XY: 700620
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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 | Invitae | Jul 13, 2018 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at