rs146872192

Variant names:

• chr19-49951946-C-A
• rs146872192
• NM_052884.3:c.1775G>T

Your query was ambiguous. Multiple possible variants found:

• chr19-49951946-C-A
• chr19-49951946-C-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.1775G>T​(p.Arg592Leu) 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. 16/21 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. R592C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SIGLEC11 NM_052884.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.725

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=0.07973921).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SIGLEC11	NM_052884.3	c.1775G>T	p.Arg592Leu	missense_variant	Exon 10 of 11	ENST00000447370.6	NP_443116.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SIGLEC11	ENST00000447370.6	c.1775G>T	p.Arg592Leu	missense_variant	Exon 10 of 11	1	NM_052884.3	ENSP00000412361.2
ENSG00000269179	ENST00000451973.1	n.*22G>T		non_coding_transcript_exon_variant	Exon 2 of 3	2		ENSP00000391489.1
ENSG00000269179	ENST00000451973.1	n.*22G>T		3_prime_UTR_variant	Exon 2 of 3	2		ENSP00000391489.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	0.33
DANN	Benign	0.93
DEOGEN2	Benign	0.0028	T;.
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.0058	N
LIST_S2	Benign	0.23	T;T
M_CAP	Benign	0.0032	T
MetaRNN	Benign	0.080	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	L;.
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.73	N;.
REVEL	Benign	0.096
Sift	Benign	0.27	T;.
Sift4G	Uncertain	0.054	T;T
Polyphen		0.012	B;B
Vest4		0.18
MutPred		0.44		Loss of MoRF binding (P = 0.0141);.;
MVP		0.25
MPC		0.011
ClinPred		0.052	T
GERP RS		-1.6
Varity_R		0.056
gMVP		0.20

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

Publications

LitVar

Other links and lift over

dbSNP: rs146872192; hg19: chr19-50455203;