19-49952338-C-A

Variant names:

• chr19-49952338-C-A
• rs767835963
• NM_052884.3:c.1708G>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.1708G>T​(p.Ala570Ser) 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. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A570T) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SIGLEC11 NM_052884.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.86
• 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=0.079663366).

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.1708G>T	p.Ala570Ser	missense	Exon 9 of 11	NP_443116.2	Q96RL6-1
	SIGLEC11	NM_001135163.1		c.1420G>T	p.Ala474Ser	missense	Exon 8 of 10	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.1708G>T	p.Ala570Ser	missense	Exon 9 of 11	ENSP00000412361.2	Q96RL6-1
	SIGLEC11	ENST00000426971.2	TSL:1	c.1420G>T	p.Ala474Ser	missense	Exon 8 of 10	ENSP00000398891.2	Q96RL6-2
	ENSG00000269179	ENST00000451973.1	TSL:2	n.110-366G>T		intron	N/A	ENSP00000391489.1	H7BZU6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

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	0.013
DANN	Benign	0.51
DEOGEN2	Benign	0.0012	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.0063	N
LIST_S2	Benign	0.39	T
M_CAP	Benign	0.0017	T
MetaRNN	Benign	0.080	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.69	N
PhyloP100		-1.9
PrimateAI	Benign	0.34	T
PROVEAN	Benign	0.31	N
REVEL	Benign	0.021
Sift	Benign	0.037	D
Sift4G	Uncertain	0.010	D
Polyphen		0.0050	B
Vest4		0.18
MutPred		0.44		Loss of helix (P = 0.1706)
MVP		0.061
MPC		0.011
ClinPred		0.14	T
GERP RS		-5.5
Varity_R		0.055
gMVP		0.11
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs767835963; hg19: chr19-50455595;