chr20-3691423-C-T

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

Scores

2
4
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.326
Variant links:
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]

Genome browser will be placed here

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
SIGLEC1NM_023068.4 linkuse as main transcriptc.4508G>A p.Arg1503His missense_variant 18/22 ENST00000344754.6
SIGLEC1NM_001367089.1 linkuse as main transcriptc.4508G>A p.Arg1503His missense_variant 17/20

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SIGLEC1ENST00000344754.6 linkuse as main transcriptc.4508G>A p.Arg1503His missense_variant 18/221 NM_023068.4 P2Q9BZZ2-1
SIGLEC1ENST00000707083.1 linkuse as main transcriptc.4508G>A p.Arg1503His missense_variant 17/20 A2
SIGLEC1ENST00000419548.4 linkuse as main transcriptc.950G>A p.Arg317His missense_variant 4/52

Frequencies

GnomAD3 genomes
AF:
0.0000263
AC:
4
AN:
152248
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000723
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000798
AC:
2
AN:
250532
Hom.:
0
AF XY:
0.0000147
AC XY:
2
AN XY:
135694
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000885
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000684
AC:
10
AN:
1460930
Hom.:
0
Cov.:
33
AF XY:
0.00000688
AC XY:
5
AN XY:
726768
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000719
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000263
AC:
4
AN:
152248
Hom.:
0
Cov.:
33
AF XY:
0.0000269
AC XY:
2
AN XY:
74388
show subpopulations
Gnomad4 AFR
AF:
0.0000723
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000113
ExAC
AF:
0.0000165
AC:
2

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 submitterclinical testingAmbry GeneticsApr 05, 2023The 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: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.11
BayesDel_addAF
Benign
-0.13
T
BayesDel_noAF
Benign
-0.32
CADD
Uncertain
23
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.23
T
Eigen
Uncertain
0.42
Eigen_PC
Uncertain
0.32
FATHMM_MKL
Benign
0.42
N
LIST_S2
Benign
0.69
T
M_CAP
Benign
0.033
D
MetaRNN
Uncertain
0.65
D
MetaSVM
Benign
-0.54
T
MutationAssessor
Pathogenic
3.0
M
MutationTaster
Benign
0.60
D;D
PrimateAI
Benign
0.45
T
PROVEAN
Benign
-2.1
N
REVEL
Benign
0.26
Sift
Benign
0.088
T
Sift4G
Uncertain
0.033
D
Polyphen
1.0
D
Vest4
0.34
MutPred
0.75
Loss of methylation at R1503 (P = 0.0532);
MVP
0.62
MPC
0.54
ClinPred
0.96
D
GERP RS
4.4
Varity_R
0.070
gMVP
0.26

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: rs777852419; hg19: chr20-3672070; API