chr20-3689187-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_023068.4(SIGLEC1):​c.5038G>A​(p.Val1680Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,860 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

SIGLEC1
NM_023068.4 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.162
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.20180482).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SIGLEC1NM_023068.4 linkuse as main transcriptc.5038G>A p.Val1680Met missense_variant 21/22 ENST00000344754.6
SIGLEC1NM_001367089.1 linkuse as main transcriptc.4997+413G>A intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SIGLEC1ENST00000344754.6 linkuse as main transcriptc.5038G>A p.Val1680Met missense_variant 21/221 NM_023068.4 P2Q9BZZ2-1
SIGLEC1ENST00000419548.4 linkuse as main transcriptc.*719G>A 3_prime_UTR_variant 5/52
SIGLEC1ENST00000707083.1 linkuse as main transcriptc.4997+413G>A intron_variant A2

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251480
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135912
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:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000879
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1461860
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
727236
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000180
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
ExAC
AF:
0.00000824
AC:
1

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 GeneticsJun 13, 2023The c.5038G>A (p.V1680M) alteration is located in exon 20 (coding exon 20) of the SIGLEC1 gene. This alteration results from a G to A substitution at nucleotide position 5038, causing the valine (V) at amino acid position 1680 to be replaced by a methionine (M). 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
-0.26
T
BayesDel_noAF
Benign
-0.60
CADD
Benign
14
DANN
Uncertain
0.99
DEOGEN2
Benign
0.093
T
Eigen
Benign
-0.41
Eigen_PC
Benign
-0.44
FATHMM_MKL
Benign
0.071
N
LIST_S2
Benign
0.71
T
M_CAP
Benign
0.0037
T
MetaRNN
Benign
0.20
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.6
L
MutationTaster
Benign
1.0
N;N
PrimateAI
Benign
0.33
T
PROVEAN
Benign
-0.17
N
REVEL
Benign
0.031
Sift
Benign
0.15
T
Sift4G
Benign
0.28
T
Polyphen
0.72
P
Vest4
0.28
MutPred
0.34
Gain of sheet (P = 0.0043);
MVP
0.42
MPC
0.13
ClinPred
0.75
D
GERP RS
2.0
Varity_R
0.041
gMVP
0.32

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.070
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: rs774832720; hg19: chr20-3669834; API