rs186522588

Variant names:

• chr19-51530720-C-T
• rs186522588
• NM_001245.7:c.667G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001245.7(SIGLEC6):​c.667G>A​(p.Gly223Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00047 in 1,614,056 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00022 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00050 (0 hom.)
• Consequence: SIGLEC6 NM_001245.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.34
• Publications: 1 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.04380402).

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.667G>A	p.Gly223Ser	missense	Exon 3 of 8	NP_001236.4
	SIGLEC6	NM_198845.6		c.667G>A	p.Gly223Ser	missense	Exon 3 of 7	NP_942142.3	O43699-3
	SIGLEC6	NM_001177547.3		c.559G>A	p.Gly187Ser	missense	Exon 3 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.667G>A	p.Gly223Ser	missense	Exon 3 of 8	ENSP00000401502.2	O43699-1
	SIGLEC6	ENST00000343300.8	TSL:1	c.667G>A	p.Gly223Ser	missense	Exon 3 of 6	ENSP00000345907.4	O43699-2
	SIGLEC6	ENST00000391797.3	TSL:1	c.634G>A	p.Gly212Ser	missense	Exon 3 of 6	ENSP00000375674.3	O43699-4

Frequencies

GnomAD3 genomes AF: 0.000223 AC: 34 AN: 152156 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000382

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000223 AC: 56 AN: 250690 AF XY: 0.000251

Gnomad AFR exome AF: 0.000187

Gnomad AMR exome AF: 0.0000579

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000423

Gnomad OTH exome AF: 0.000164

GnomAD4 exome AF: 0.000496 AC: 725 AN: 1461782 Hom.: 0 Cov.: 34 AF XY: 0.000476 AC XY: 346 AN XY: 727208

African (AFR) AF: 0.0000597 AC: 2 AN: 33478

American (AMR) AF: 0.000179 AC: 8 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26116

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.0000580 AC: 5 AN: 86256

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.000617 AC: 686 AN: 1111966

Other (OTH) AF: 0.000364 AC: 22 AN: 60382

GnomAD4 genome AF: 0.000223 AC: 34 AN: 152274 Hom.: 0 Cov.: 32 AF XY: 0.0000806 AC XY: 6 AN XY: 74436

African (AFR) AF: 0.000120 AC: 5 AN: 41560

American (AMR) AF: 0.000196 AC: 3 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5164

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000382 AC: 26 AN: 68024

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.000233 Hom.: 0

Bravo AF: 0.000246

TwinsUK AF: 0.00135 AC: 5

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.000454 AC: 2

ESP6500EA AF: 0.00105 AC: 9

ExAC AF: 0.000214 AC: 26

EpiCase AF: 0.000382

EpiControl AF: 0.000534

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	0.11
BayesDel_addAF	Benign	-0.53	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	2.0
DANN	Benign	0.90
DEOGEN2	Benign	0.024	T
Eigen	Benign	-0.74
Eigen_PC	Benign	-0.87
FATHMM_MKL	Benign	0.0060	N
LIST_S2	Benign	0.55	T
M_CAP	Benign	0.0059	T
MetaRNN	Benign	0.044	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Pathogenic	3.2	M
PhyloP100		-1.3
PrimateAI	Benign	0.35	T
PROVEAN	Uncertain	-2.8	D
REVEL	Benign	0.036
Sift	Benign	0.20	T
Sift4G	Benign	0.14	T
Polyphen		0.66	P
Vest4		0.17
MVP		0.11
MPC		0.57
ClinPred		0.087	T
GERP RS		1.2
Varity_R		0.066
gMVP		0.27
Mutation Taster		=95/5	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

dbSNP: rs186522588; hg19: chr19-52033974; COSMIC: COSV104660983; COSMIC: COSV104660983;