chr19-51125732-C-T

Variant names:

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

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>T​(p.Ser186Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000049 in 1,613,634 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000059 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000048 (0 hom.)
• Consequence: SIGLEC9 NM_014441.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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=0.11222696).

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>T	p.Ser186Phe	missense	Exon 2 of 7	NP_055256.1	Q9Y336-1
	SIGLEC9	NM_001198558.1		c.557C>T	p.Ser186Phe	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>T	p.Ser186Phe	missense	Exon 2 of 7	ENSP00000250360.2	Q9Y336-1
	SIGLEC9	ENST00000850850.1		c.557C>T	p.Ser186Phe	missense	Exon 2 of 8	ENSP00000520939.1	A0ABJ7H2Z3
	SIGLEC9	ENST00000966614.1		c.557C>T	p.Ser186Phe	missense	Exon 2 of 8	ENSP00000636673.1

Frequencies

GnomAD3 genomes AF: 0.0000592 AC: 9 AN: 152130 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000279 AC: 7 AN: 251298 AF XY: 0.00000736

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000440

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.0000479 AC: 70 AN: 1461504 Hom.: 0 Cov.: 33 AF XY: 0.0000454 AC XY: 33 AN XY: 727070

African (AFR) AF: 0.0000299 AC: 1 AN: 33472

American (AMR) AF: 0.0000224 AC: 1 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26122

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000348 AC: 3 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53382

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000567 AC: 63 AN: 1111702

Other (OTH) AF: 0.0000331 AC: 2 AN: 60386

GnomAD4 genome AF: 0.0000592 AC: 9 AN: 152130 Hom.: 0 Cov.: 32 AF XY: 0.0000673 AC XY: 5 AN XY: 74296

African (AFR) AF: 0.00 AC: 0 AN: 41410

American (AMR) AF: 0.000262 AC: 4 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: 0.000207 AC: 1 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: 0.0000588 AC: 4 AN: 68018

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

Alfa AF: 0.0000386 Hom.: 0

Bravo AF: 0.0000453

ExAC AF: 0.0000165 AC: 2

EpiCase AF: 0.000109

EpiControl AF: 0.0000593

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	0.13
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	6.8
DANN	Uncertain	0.98
DEOGEN2	Benign	0.046	T
Eigen	Benign	-0.77
Eigen_PC	Benign	-0.90
FATHMM_MKL	Benign	0.027	N
LIST_S2	Benign	0.53	T
M_CAP	Benign	0.0050	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		-0.37
PrimateAI	Benign	0.25	T
PROVEAN	Uncertain	-4.2	D
REVEL	Benign	0.047
Sift	Uncertain	0.028	D
Sift4G	Benign	0.34	T
Polyphen		0.047	B
Vest4		0.15
MVP		0.22
MPC		0.24
ClinPred		0.078	T
GERP RS		1.8
Varity_R		0.076
gMVP		0.12
Mutation Taster		=95/5	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: COSV51582602; COSMIC: COSV51582602;