NM_014441.3:c.236C>T

Variant names:

• chr19-51125210-C-T
• NM_014441.3:c.236C>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.236C>T​(p.Pro79Leu) 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. 13/22 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: SIGLEC9 NM_014441.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.97
• Publications: 0 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=0.21618158).

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.236C>T	p.Pro79Leu	missense	Exon 1 of 7	NP_055256.1	Q9Y336-1
	SIGLEC9	NM_001198558.1		c.236C>T	p.Pro79Leu	missense	Exon 1 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.236C>T	p.Pro79Leu	missense	Exon 1 of 7	ENSP00000250360.2	Q9Y336-1
	SIGLEC9	ENST00000850850.1		c.236C>T	p.Pro79Leu	missense	Exon 1 of 8	ENSP00000520939.1	A0ABJ7H2Z3
	SIGLEC9	ENST00000966614.1		c.236C>T	p.Pro79Leu	missense	Exon 1 of 8	ENSP00000636673.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

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	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	11
DANN	Uncertain	0.99
DEOGEN2	Benign	0.10	T
Eigen	Benign	-0.42
Eigen_PC	Benign	-0.68
FATHMM_MKL	Benign	0.069	N
LIST_S2	Benign	0.62	T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		-2.0
PrimateAI	Benign	0.34	T
PROVEAN	Pathogenic	-8.9	D
REVEL	Benign	0.074
Sift	Uncertain	0.021	D
Sift4G	Uncertain	0.052	T
Polyphen		0.90	P
Vest4		0.096
MutPred		0.53		Loss of disorder (P = 0.0345)
MVP		0.54
MPC		0.72
ClinPred		0.89	D
GERP RS		0.64
PromoterAI		-0.046	Neutral
Varity_R		0.17
gMVP		0.20
Mutation Taster		=98/2	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

hg19: chr19-51628467;