19-51528241-C-G

Variant names:

• chr19-51528241-C-G
• rs1323409813
• NM_001245.7:c.1025G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001245.7(SIGLEC6):​c.1025G>C​(p.Gly342Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,718 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G342V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SIGLEC6 NM_001245.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.302
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05591768).

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.1025G>C	p.Gly342Ala	missense	Exon 6 of 8	NP_001236.4
	SIGLEC6	NM_198845.6		c.977G>C	p.Gly326Ala	missense	Exon 5 of 7	NP_942142.3	O43699-3
	SIGLEC6	NM_001177547.3		c.869G>C	p.Gly290Ala	missense	Exon 5 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.1025G>C	p.Gly342Ala	missense	Exon 6 of 8	ENSP00000401502.2	O43699-1
	SIGLEC6	ENST00000343300.8	TSL:1	c.1012+1483G>C		intron	N/A	ENSP00000345907.4	O43699-2
	SIGLEC6	ENST00000391797.3	TSL:1	c.979+1483G>C		intron	N/A	ENSP00000375674.3	O43699-4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461718 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727184

African (AFR) AF: 0.0000299 AC: 1 AN: 33476

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111858

Other (OTH) AF: 0.00 AC: 0 AN: 60388

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	0.66
DANN	Benign	0.12
DEOGEN2	Benign	0.00055	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.00033	N
LIST_S2	Benign	0.47	T
M_CAP	Benign	0.0033	T
MetaRNN	Benign	0.056	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.55	N
PhyloP100		0.30
PrimateAI	Benign	0.30	T
PROVEAN	Pathogenic	-4.4	D
REVEL	Benign	0.062
Sift	Uncertain	0.0040	D
Sift4G	Benign	0.29	T
Polyphen		0.0090	B
Vest4		0.14
MutPred		0.36		Loss of methylation at K339 (P = 0.0882)
MVP		0.067
MPC		0.20
ClinPred		0.58	D
GERP RS		0.52
Varity_R		0.041
gMVP		0.081
Mutation Taster		=99/1	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: rs1323409813; hg19: chr19-52031495;