chr20-3691423-C-T
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_023068.4(SIGLEC1):c.4508G>A(p.Arg1503His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000868 in 1,613,178 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000068 ( 0 hom. )
Consequence
SIGLEC1
NM_023068.4 missense
NM_023068.4 missense
Scores
2
4
13
Clinical Significance
Conservation
PhyloP100: 0.326
Genes affected
SIGLEC1 (HGNC:11127): (sialic acid binding Ig like lectin 1) This gene encodes a member of the immunoglobulin superfamily. The encoded protein is a lectin-like adhesion molecule that binds glycoconjugate ligands on cell surfaces in a sialic acid-dependent manner. It is a type I transmembrane protein expressed only by a subpopulation of macrophages and is involved in mediating cell-cell interactions. The protein plays an important role in multiple human diseases and bacterial and viral infections has been shown to enhance SARS-CoV-2 infection. [provided by RefSeq, Dec 2021]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SIGLEC1 | NM_023068.4 | c.4508G>A | p.Arg1503His | missense_variant | 18/22 | ENST00000344754.6 | |
SIGLEC1 | NM_001367089.1 | c.4508G>A | p.Arg1503His | missense_variant | 17/20 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SIGLEC1 | ENST00000344754.6 | c.4508G>A | p.Arg1503His | missense_variant | 18/22 | 1 | NM_023068.4 | P2 | |
SIGLEC1 | ENST00000707083.1 | c.4508G>A | p.Arg1503His | missense_variant | 17/20 | A2 | |||
SIGLEC1 | ENST00000419548.4 | c.950G>A | p.Arg317His | missense_variant | 4/5 | 2 |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152248Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.00000798 AC: 2AN: 250532Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135694
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GnomAD4 exome AF: 0.00000684 AC: 10AN: 1460930Hom.: 0 Cov.: 33 AF XY: 0.00000688 AC XY: 5AN XY: 726768
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GnomAD4 genome AF: 0.0000263 AC: 4AN: 152248Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74388
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 05, 2023 | The c.4508G>A (p.R1503H) alteration is located in exon 17 (coding exon 17) of the SIGLEC1 gene. This alteration results from a G to A substitution at nucleotide position 4508, causing the arginine (R) at amino acid position 1503 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Pathogenic
DEOGEN2
Benign
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Benign
N
LIST_S2
Benign
T
M_CAP
Benign
D
MetaRNN
Uncertain
D
MetaSVM
Benign
T
MutationAssessor
Pathogenic
M
MutationTaster
Benign
D;D
PrimateAI
Benign
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Benign
T
Sift4G
Uncertain
D
Polyphen
D
Vest4
MutPred
Loss of methylation at R1503 (P = 0.0532);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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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