19-51529892-C-T

Variant names:

• chr19-51529892-C-T
• NM_001245.7:c.844G>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001245.7(SIGLEC6):​c.844G>A​(p.Ala282Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 0.946
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001245.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SIGLEC6	NM_001245.7	MANE Select	c.844G>A	p.Ala282Thr	missense	Exon 5 of 8	NP_001236.4
	SIGLEC6	NM_198845.6		c.796G>A	p.Ala266Thr	missense	Exon 4 of 7	NP_942142.3	O43699-3
	SIGLEC6	NM_001177547.3		c.688G>A	p.Ala230Thr	missense	Exon 4 of 7	NP_001171018.1	O43699-6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SIGLEC6	ENST00000425629.8	TSL:2 MANE Select	c.844G>A	p.Ala282Thr	missense	Exon 5 of 8	ENSP00000401502.2	O43699-1
	SIGLEC6	ENST00000343300.8	TSL:1	c.844G>A	p.Ala282Thr	missense	Exon 5 of 6	ENSP00000345907.4	O43699-2
	SIGLEC6	ENST00000391797.3	TSL:1	c.811G>A	p.Ala271Thr	missense	Exon 5 of 6	ENSP00000375674.3	O43699-4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 37

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Uncertain	0.044	T
BayesDel_noAF	Benign	-0.18
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.043	T
Eigen	Uncertain	0.36
Eigen_PC	Benign	0.20
FATHMM_MKL	Benign	0.45	N
LIST_S2	Benign	0.85	D
M_CAP	Uncertain	0.14	D
MetaRNN	Uncertain	0.49	T
MetaSVM	Uncertain	-0.14	T
MutationAssessor	Pathogenic	3.4	M
PhyloP100		0.95
PrimateAI	Benign	0.35	T
PROVEAN	Uncertain	-3.8	D
REVEL	Uncertain	0.41
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.016	D
Polyphen		0.98	D
Vest4		0.35
MutPred		0.60		Gain of glycosylation at A282 (P = 0.1205)
MVP		0.78
MPC		0.62
ClinPred		0.99	D
GERP RS		3.7
Varity_R		0.60
gMVP		0.15
Mutation Taster		=81/19	polymorphism

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

Other links and lift over

hg19: chr19-52033146;