chr19-51520177-C-T

Variant names:

• chr19-51520177-C-T
• NM_001245.7:c.1267G>A

Variant summary

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

The NM_001245.7(SIGLEC6):​c.1267G>A​(p.Glu423Lys) 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. 12/21 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: 1.29

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]

ENSG00000268777 (HGNC:):

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=0.21054009).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SIGLEC6	NM_001245.7	c.1267G>A	p.Glu423Lys	missense_variant	Exon 8 of 8	ENST00000425629.8	NP_001236.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SIGLEC6	ENST00000425629.8	c.1267G>A	p.Glu423Lys	missense_variant	Exon 8 of 8	2	NM_001245.7	ENSP00000401502.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 30, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1267G>A (p.E423K) alteration is located in exon 8 (coding exon 8) of the SIGLEC6 gene. This alteration results from a G to A substitution at nucleotide position 1267, causing the glutamic acid (E) at amino acid position 423 to be replaced by a lysine (K). 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	0.13
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	18
DANN	Uncertain	1.0
DEOGEN2	Benign	0.026	.;.;T
Eigen	Benign	-0.010
Eigen_PC	Benign	-0.30
FATHMM_MKL	Benign	0.033	N
LIST_S2	Benign	0.82	T;T;D
M_CAP	Benign	0.0060	T
MetaRNN	Benign	0.21	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	2.9	.;.;M
PrimateAI	Benign	0.42	T
PROVEAN	Uncertain	-3.1	.;D;D
REVEL	Benign	0.069
Sift	Uncertain	0.0030	.;D;D
Sift4G	Uncertain	0.0030	D;D;D
Polyphen		1.0	D;.;D
Vest4		0.21
MutPred		0.45		.;.;Gain of ubiquitination at E423 (P = 0.0075);
MVP		0.17
MPC		0.17
ClinPred		0.86	D
GERP RS		2.6
Varity_R		0.23
gMVP		0.44

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: chr19-52023431;