19-49958418-T-A

Variant names:

• chr19-49958418-T-A
• rs749874555
• NM_052884.3:c.1516A>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_052884.3(SIGLEC11):​c.1516A>T​(p.Thr506Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000889 in 1,461,646 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 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)
  • Exomes 𝑓: 0.0000089 (0 hom.)
• Consequence: SIGLEC11 NM_052884.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.163

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14059955).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SIGLEC11	NM_052884.3	c.1516A>T	p.Thr506Ser	missense_variant	Exon 8 of 11	ENST00000447370.6	NP_443116.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SIGLEC11	ENST00000447370.6	c.1516A>T	p.Thr506Ser	missense_variant	Exon 8 of 11	1	NM_052884.3	ENSP00000412361.2
SIGLEC11	ENST00000426971.2	c.1363+225A>T		intron_variant	Intron 7 of 9	1		ENSP00000398891.2
SIGLEC11	ENST00000426296.1	n.40A>T		non_coding_transcript_exon_variant	Exon 1 of 3	2		ENSP00000407387.1
ENSG00000269179	ENST00000451973.1	n.-27A>T		upstream_gene_variant		2		ENSP00000391489.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000400 AC: 1 AN: 249782 Hom.: 0 AF XY: 0.00000739 AC XY: 1 AN XY: 135326

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 SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000887

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000889 AC: 13 AN: 1461646 Hom.: 0 Cov.: 32 AF XY: 0.00000413 AC XY: 3 AN XY: 727142

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000989

Gnomad4 OTH exome AF: 0.0000331

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 25, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1516A>T (p.T506S) alteration is located in exon 8 (coding exon 8) of the SIGLEC11 gene. This alteration results from a A to T substitution at nucleotide position 1516, causing the threonine (T) at amino acid position 506 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	9.1
DANN	Benign	0.96
DEOGEN2	Benign	0.020	T
Eigen	Benign	-0.42
Eigen_PC	Benign	-0.69
FATHMM_MKL	Benign	0.023	N
LIST_S2	Benign	0.31	T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.14	T
MetaSVM	Uncertain	-0.21	T
MutationAssessor	Uncertain	2.0	M
PROVEAN	Benign	-1.9	N
REVEL	Uncertain	0.32
Sift	Benign	0.34	T
Sift4G	Benign	0.066	T
Polyphen		0.94	P
Vest4		0.14
MutPred		0.17		Gain of sheet (P = 0.039);
MVP		0.78
MPC		0.069
ClinPred		0.18	T
GERP RS		0.24
Varity_R		0.11
gMVP		0.11

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs749874555; hg19: chr19-50461675;