19-51124992-G-T

Variant names:

• chr19-51124992-G-T
• rs200563478
• NM_014441.3:c.18G>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_014441.3(SIGLEC9):​c.18G>T​(p.Leu6Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,455,404 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. L6L) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: SIGLEC9 NM_014441.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.489
• 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP7: Synonymous conserved (PhyloP=0.489 with no splicing effect.

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.18G>T	p.Leu6Leu	synonymous	Exon 1 of 7	NP_055256.1	Q9Y336-1
	SIGLEC9	NM_001198558.1		c.18G>T	p.Leu6Leu	synonymous	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.18G>T	p.Leu6Leu	synonymous	Exon 1 of 7	ENSP00000250360.2	Q9Y336-1
	SIGLEC9	ENST00000850850.1		c.18G>T	p.Leu6Leu	synonymous	Exon 1 of 8	ENSP00000520939.1	A0ABJ7H2Z3
	SIGLEC9	ENST00000966614.1		c.18G>T	p.Leu6Leu	synonymous	Exon 1 of 8	ENSP00000636673.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1455404 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 723710

African (AFR) AF: 0.00 AC: 0 AN: 33454

American (AMR) AF: 0.00 AC: 0 AN: 44446

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25480

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.00 AC: 0 AN: 85214

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53008

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5728

European-Non Finnish (NFE) AF: 9.02e-7 AC: 1 AN: 1108240

Other (OTH) AF: 0.00 AC: 0 AN: 60142

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.2
DANN	Benign	0.62
PhyloP100		0.49
PromoterAI		0.34	Neutral

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: rs200563478; hg19: chr19-51628249;