19-51530698-A-G
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001245.7(SIGLEC6):c.689T>C(p.Ile230Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000126 in 1,613,582 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00013 ( 0 hom. )
Consequence
SIGLEC6
NM_001245.7 missense
NM_001245.7 missense
Scores
1
4
11
Clinical Significance
Conservation
PhyloP100: 2.20
Genes affected
SIGLEC6 (HGNC:10875): (sialic acid binding Ig like lectin 6) This gene encodes a member of the SIGLEC (sialic acid binding immunoglobulin-like lectin) family of proteins. The encoded transmembrane receptor binds sialyl-TN glycans and leptin. Placental expression of the encoded protein is upregulated in preeclampsia. [provided by RefSeq, Jul 2016]
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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=0.21692303).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SIGLEC6 | NM_001245.7 | c.689T>C | p.Ile230Thr | missense_variant | 3/8 | ENST00000425629.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SIGLEC6 | ENST00000425629.8 | c.689T>C | p.Ile230Thr | missense_variant | 3/8 | 2 | NM_001245.7 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000658 AC: 10AN: 151886Hom.: 0 Cov.: 32
GnomAD3 genomes
?
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GnomAD3 exomes AF: 0.0000320 AC: 8AN: 250344Hom.: 0 AF XY: 0.0000295 AC XY: 4AN XY: 135548
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GnomAD4 exome AF: 0.000132 AC: 193AN: 1461696Hom.: 0 Cov.: 34 AF XY: 0.000136 AC XY: 99AN XY: 727166
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GnomAD4 genome ? AF: 0.0000658 AC: 10AN: 151886Hom.: 0 Cov.: 32 AF XY: 0.0000270 AC XY: 2AN XY: 74166
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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 | May 04, 2022 | The c.689T>C (p.I230T) alteration is located in exon 3 (coding exon 3) of the SIGLEC6 gene. This alteration results from a T to C substitution at nucleotide position 689, causing the isoleucine (I) at amino acid position 230 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T;T;T;T;T;T
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Pathogenic
H;H;.;H;H;.
MutationTaster
Benign
N;N;N;N;N;N
PrimateAI
Uncertain
T
REVEL
Benign
Sift4G
Uncertain
D;D;D;D;D;D
Polyphen
P;.;.;D;P;P
Vest4
MVP
MPC
0.43
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