chr19-49958418-T-A

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 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. 13/21 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
• 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 0 ACMG points.

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

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.1516A>T	p.Thr506Ser	missense	Exon 8 of 11	NP_443116.2	Q96RL6-1
	SIGLEC11	NM_001135163.1		c.1363+225A>T		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.1516A>T	p.Thr506Ser	missense	Exon 8 of 11	ENSP00000412361.2	Q96RL6-1
	SIGLEC11	ENST00000426971.2	TSL:1	c.1363+225A>T		intron	N/A	ENSP00000398891.2	Q96RL6-2
	SIGLEC11	ENST00000959926.1		c.1252A>T	p.Thr418Ser	missense	Exon 7 of 10	ENSP00000629985.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000400 AC: 1 AN: 249782 AF XY: 0.00000739

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: 0.00000887

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

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44704

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26116

East Asian (EAS) AF: 0.00 AC: 0 AN: 39690

South Asian (SAS) AF: 0.00 AC: 0 AN: 86236

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53340

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 0.00000989 AC: 11 AN: 1111950

Other (OTH) AF: 0.0000331 AC: 2 AN: 60372

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

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	0.11
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
PhyloP100		-0.16
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
Mutation Taster		=90/10	polymorphism

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

Other links and lift over

dbSNP: rs749874555; hg19: chr19-50461675;