NM_052884.3:c.1615G>C

Variant names:

• chr19-49958319-C-G
• rs767478430
• NM_052884.3:c.1615G>C

Variant summary

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

The NM_052884.3(SIGLEC11):​c.1615G>C​(p.Gly539Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,864 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SIGLEC11 NM_052884.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.343
• Publications: 0 publications found

Genes affected

SIGLEC11 (HGNC:15622): (sialic acid binding Ig like lectin 11) This gene encodes a member of the sialic acid-binding immunoglobulin-like lectin family. These cell surface lectins are characterized by structural motifs in the immunoglobulin (Ig)-like domains and sialic acid recognition sites in the first Ig V set domain. This family member mediates anti-inflammatory and immunosuppressive signaling. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2011]

ENSG00000269179 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_052884.3. 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
	SIGLEC11	NM_052884.3	MANE Select	c.1615G>C	p.Gly539Arg	missense	Exon 8 of 11	NP_443116.2	Q96RL6-1
	SIGLEC11	NM_001135163.1		c.1363+324G>C		intron	N/A	NP_001128635.1	Q96RL6-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SIGLEC11	ENST00000447370.6	TSL:1 MANE Select	c.1615G>C	p.Gly539Arg	missense	Exon 8 of 11	ENSP00000412361.2	Q96RL6-1
	SIGLEC11	ENST00000426971.2	TSL:1	c.1363+324G>C		intron	N/A	ENSP00000398891.2	Q96RL6-2
	ENSG00000269179	ENST00000451973.1	TSL:2	n.73G>C		non_coding_transcript_exon	Exon 1 of 3	ENSP00000391489.1	H7BZU6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000401 AC: 1 AN: 249552 AF XY: 0.00

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: 0.00000891

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461864 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727234

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53412

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

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1112004

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Benign	-0.090
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.25	T
Eigen	Benign	-0.25
Eigen_PC	Benign	-0.57
FATHMM_MKL	Benign	0.012	N
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.013	T
MetaRNN	Uncertain	0.65	D
MetaSVM	Uncertain	-0.044	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		-0.34
PROVEAN	Pathogenic	-5.3	D
REVEL	Uncertain	0.41
Sift	Benign	0.13	T
Sift4G	Benign	0.069	T
Polyphen		1.0	D
Vest4		0.36
MutPred		0.72		Gain of MoRF binding (P = 0.0204)
MVP		0.85
MPC		0.075
ClinPred		0.96	D
GERP RS		0.11
Varity_R		0.29
gMVP		0.58
Mutation Taster		=90/10	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: rs767478430; hg19: chr19-50461576;