chr19-51531277-A-G
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_001245.7(SIGLEC6):c.310T>C(p.Cys104Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,860 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000034 ( 0 hom. )
Consequence
SIGLEC6
NM_001245.7 missense
NM_001245.7 missense
Scores
4
6
6
Clinical Significance
Conservation
PhyloP100: 3.48
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 Likely_pathogenic. Variant got 6 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.955
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SIGLEC6 | NM_001245.7 | c.310T>C | p.Cys104Arg | missense_variant | 2/8 | ENST00000425629.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SIGLEC6 | ENST00000425629.8 | c.310T>C | p.Cys104Arg | missense_variant | 2/8 | 2 | NM_001245.7 | P2 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD3 exomes AF: 0.00000399 AC: 1AN: 250646Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135732
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GnomAD4 exome AF: 0.00000342 AC: 5AN: 1461860Hom.: 0 Cov.: 36 AF XY: 0.00000138 AC XY: 1AN XY: 727242
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GnomAD4 genome ? Cov.: 32
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32
Bravo
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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 | Dec 19, 2023 | The c.310T>C (p.C104R) alteration is located in exon 2 (coding exon 2) of the SIGLEC6 gene. This alteration results from a T to C substitution at nucleotide position 310, causing the cysteine (C) at amino acid position 104 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
Eigen
Uncertain
Eigen_PC
Benign
FATHMM_MKL
Benign
D
LIST_S2
Benign
T;T;T;T;T;T
M_CAP
Benign
D
MetaRNN
Pathogenic
D;D;D;D;D;D
MetaSVM
Uncertain
T
MutationAssessor
Pathogenic
M;M;.;M;M;M
MutationTaster
Benign
D;D;D;D;D;D
PrimateAI
Uncertain
T
REVEL
Uncertain
Sift4G
Pathogenic
D;D;D;D;D;D
Polyphen
D;.;.;D;D;D
Vest4
MutPred
Gain of disorder (P = 0.0032);Gain of disorder (P = 0.0032);.;Gain of disorder (P = 0.0032);Gain of disorder (P = 0.0032);Gain of disorder (P = 0.0032);
MVP
MPC
0.85
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