19-51531268-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001245.7(SIGLEC6):c.319A>G(p.Ser107Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 32)
• Consequence: SIGLEC6 NM_001245.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.81

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]

ACMG classification

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=0.1853697).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SIGLEC6	NM_001245.7	c.319A>G	p.Ser107Gly	missense_variant	2/8	ENST00000425629.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SIGLEC6	ENST00000425629.8	c.319A>G	p.Ser107Gly	missense_variant	2/8	2	NM_001245.7	P2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 03, 2024

The c.319A>G (p.S107G) alteration is located in exon 2 (coding exon 2) of the SIGLEC6 gene. This alteration results from a A to G substitution at nucleotide position 319, causing the serine (S) at amino acid position 107 to be replaced by a glycine (G). 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	0.15
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
Cadd	Benign	6.2
Dann	Benign	0.85
Eigen	Benign	-0.86
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.0033	N
LIST_S2	Benign	0.13	T;T;T;T;T;T
M_CAP	Benign	0.025	D
MetaRNN	Benign	0.19	T;T;T;T;T;T
MetaSVM	Benign	-0.75	T
MutationAssessor	Uncertain	2.2	M;M;.;M;M;M
MutationTaster	Benign	1.0	N;N;N;N;N;N
PrimateAI	Benign	0.35	T
REVEL	Benign	0.068
Sift4G	Benign	0.36	T;T;T;T;T;T
Polyphen		0.46	P;.;.;B;D;P
Vest4		0.12
MutPred		0.37		Loss of phosphorylation at S107 (P = 0.0231);Loss of phosphorylation at S107 (P = 0.0231);.;Loss of phosphorylation at S107 (P = 0.0231);Loss of phosphorylation at S107 (P = 0.0231);Loss of phosphorylation at S107 (P = 0.0231);
MVP		0.62
MPC		0.15
ClinPred		0.36	T
GERP RS		-1.4
Varity_R		0.14
gMVP		0.40

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-52034522;