rs1364652112
Variant names:
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_053003.4(SIGLEC12):c.1601G>T(p.Gly534Val) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000658 in 151,900 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/24 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
SIGLEC12
NM_053003.4 missense, splice_region
NM_053003.4 missense, splice_region
Scores
1
3
14
Splicing: ADA: 0.00001907
2
Clinical Significance
Conservation
PhyloP100: -0.333
Publications
1 publications found
Genes affected
SIGLEC12 (HGNC:15482): (sialic acid binding Ig like lectin 12) Sialic acid-binding immunoglobulin-like lectins (SIGLECs) are a family of cell surface proteins belonging to the immunoglobulin superfamily. They mediate protein-carbohydrate interactions by selectively binding to different sialic acid moieties present on glycolipids and glycoproteins. This gene encodes a member of the SIGLEC3-like subfamily of SIGLECs. Members of this subfamily are characterized by an extracellular V-set immunoglobulin-like domain followed by two C2-set immunoglobulin-like domains, and the cytoplasmic tyrosine-based motifs ITIM and SLAM-like. The encoded protein, upon tyrosine phosphorylation, has been shown to recruit the Src homology 2 domain-containing protein-tyrosine phosphatases SHP1 and SHP2. It has been suggested that the protein is involved in the negative regulation of macrophage signaling by functioning as an inhibitory receptor. This gene is located in a cluster with other SIGLEC3-like genes on 19q13.4. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2013]
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ACMG classification
Classification was made for transcript
Our verdict: Uncertain_significance. The variant received 0 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.07897872).
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_053003.4. You can select a different transcript below to see updated ACMG assignments.
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| SIGLEC12 | TSL:1 MANE Select | c.1601G>T | p.Gly534Val | missense splice_region | Exon 8 of 8 | ENSP00000291707.3 | Q96PQ1-1 | ||
| SIGLEC12 | TSL:1 | n.*816G>T | splice_region non_coding_transcript_exon | Exon 8 of 8 | ENSP00000469791.1 | M0QYF3 | |||
| SIGLEC12 | TSL:1 | n.*816G>T | 3_prime_UTR | Exon 8 of 8 | ENSP00000469791.1 | M0QYF3 |
Frequencies
GnomAD3 genomes 0.00000658 AC: 1AN: 151900Hom.: 0 Cov.: 31 show subpopulations
GnomAD3 genomes
AF:
AC:
1
AN:
151900
Hom.:
Cov.:
31
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1401368Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 691460
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
AC:
0
AN:
1401368
Hom.:
Cov.:
31
AF XY:
AC XY:
0
AN XY:
691460
African (AFR)
AF:
AC:
0
AN:
31844
American (AMR)
AF:
AC:
0
AN:
38394
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
22220
East Asian (EAS)
AF:
AC:
0
AN:
39214
South Asian (SAS)
AF:
AC:
0
AN:
76946
European-Finnish (FIN)
AF:
AC:
0
AN:
44486
Middle Eastern (MID)
AF:
AC:
0
AN:
5334
European-Non Finnish (NFE)
AF:
AC:
0
AN:
1084900
Other (OTH)
AF:
AC:
0
AN:
58030
GnomAD4 genome 0.00000658 AC: 1AN: 151900Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 74150 show subpopulations
GnomAD4 genome
AF:
AC:
1
AN:
151900
Hom.:
Cov.:
31
AF XY:
AC XY:
0
AN XY:
74150
show subpopulations
African (AFR)
AF:
AC:
0
AN:
41346
American (AMR)
AF:
AC:
0
AN:
15256
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3468
East Asian (EAS)
AF:
AC:
0
AN:
5180
South Asian (SAS)
AF:
AC:
0
AN:
4806
European-Finnish (FIN)
AF:
AC:
0
AN:
10552
Middle Eastern (MID)
AF:
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
AC:
1
AN:
67974
Other (OTH)
AF:
AC:
0
AN:
2090
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.525
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
Hom.:
Bravo
AF:
Asia WGS
AF:
AC:
1
AN:
3478
ClinVar
ClinVar submissions
View on ClinVar Significance:Uncertain significance
Revision:criteria provided, single submitter
Pathogenic
VUS
Benign
Condition
-
1
-
not specified (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
DANN
Benign
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T
M_CAP
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M
PhyloP100
PrimateAI
Benign
T
PROVEAN
Pathogenic
D
REVEL
Benign
Sift
Uncertain
D
Sift4G
Uncertain
D
Polyphen
B
Vest4
MutPred
Loss of catalytic residue at G534 (P = 0.1381)
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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