19-51125732-C-A

Variant names:

• chr19-51125732-C-A
• rs764072934
• NM_014441.3:c.557C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014441.3(SIGLEC9):​c.557C>A​(p.Ser186Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,130 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. 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. S186F) has been classified as Uncertain significance.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: SIGLEC9 NM_014441.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.369
• Publications: 4 publications found

Genes affected

SIGLEC9 (HGNC:10878): (sialic acid binding Ig like lectin 9) Predicted to enable monosaccharide binding activity and sialic acid binding activity. Predicted to be involved in cell adhesion. Predicted to act upstream of or within negative regulation of inflammatory response and negative regulation of phagocytosis, engulfment. Predicted to be located in external side of plasma membrane. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000268595 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19853339).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014441.3. 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
	SIGLEC9	NM_014441.3	MANE Select	c.557C>A	p.Ser186Tyr	missense	Exon 2 of 7	NP_055256.1	Q9Y336-1
	SIGLEC9	NM_001198558.1		c.557C>A	p.Ser186Tyr	missense	Exon 2 of 7	NP_001185487.1	Q9Y336-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SIGLEC9	ENST00000250360.8	TSL:1 MANE Select	c.557C>A	p.Ser186Tyr	missense	Exon 2 of 7	ENSP00000250360.2	Q9Y336-1
	SIGLEC9	ENST00000850850.1		c.557C>A	p.Ser186Tyr	missense	Exon 2 of 8	ENSP00000520939.1	A0ABJ7H2Z3
	SIGLEC9	ENST00000966614.1		c.557C>A	p.Ser186Tyr	missense	Exon 2 of 8	ENSP00000636673.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152130 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 33

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152130 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74296

African (AFR) AF: 0.0000241 AC: 1 AN: 41410

American (AMR) AF: 0.00 AC: 0 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68018

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	16
DANN	Benign	0.90
DEOGEN2	Benign	0.039	T
Eigen	Benign	-0.40
Eigen_PC	Benign	-0.64
FATHMM_MKL	Benign	0.022	N
LIST_S2	Benign	0.67	T
M_CAP	Benign	0.0044	T
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		-0.37
PrimateAI	Benign	0.26	T
PROVEAN	Uncertain	-4.2	D
REVEL	Benign	0.052
Sift	Uncertain	0.0010	D
Sift4G	Benign	0.55	T
Polyphen		0.84	P
Vest4		0.25
MutPred		0.43		Loss of disorder (P = 0.0016)
MVP		0.22
MPC		0.67
ClinPred		0.46	T
GERP RS		1.8
Varity_R		0.11
gMVP		0.13
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: rs764072934; hg19: chr19-51628989; COSMIC: COSV51583355; COSMIC: COSV51583355;