19-51529892-C-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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

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 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SIGLEC6	NM_001245.7	c.844G>A	p.Ala282Thr	missense_variant	Exon 5 of 8	ENST00000425629.8	NP_001236.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SIGLEC6	ENST00000425629.8	c.844G>A	p.Ala282Thr	missense_variant	Exon 5 of 8	2	NM_001245.7	ENSP00000401502.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 37

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 29, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.844G>A (p.A282T) alteration is located in exon 5 (coding exon 5) of the SIGLEC6 gene. This alteration results from a G to A substitution at nucleotide position 844, causing the alanine (A) at amino acid position 282 to be replaced by a threonine (T). 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	0.17
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;D;D;T;D;T
M_CAP	Uncertain	0.14	D
MetaRNN	Uncertain	0.49	T;T;T;T;T;T
MetaSVM	Uncertain	-0.14	T
MutationAssessor	Pathogenic	3.4	.;.;.;M;M;.
PrimateAI	Benign	0.35	T
PROVEAN	Uncertain	-3.8	.;D;D;D;D;.
REVEL	Uncertain	0.41
Sift	Pathogenic	0.0	.;D;D;D;D;.
Sift4G	Uncertain	0.016	D;D;D;D;D;D
Polyphen		0.98	D;.;.;D;D;D
Vest4		0.35
MutPred		0.60		.;.;.;Gain of glycosylation at A282 (P = 0.1205);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

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: chr19-52033146;