rs373704230

Variant names:

• chr19-49950025-C-T
• rs373704230
• NM_052884.3:c.2042G>A

Your query was ambiguous. Multiple possible variants found:

• chr19-49950025-C-T
• chr19-49950025-C-A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_052884.3(SIGLEC11):​c.2042G>A​(p.Gly681Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000427 in 1,545,666 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00023 (1 hom., cov: 31)
  • Exomes 𝑓: 0.000022 (0 hom.)
• Consequence: SIGLEC11 NM_052884.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.49
• 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.03400153).

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.2042G>A	p.Gly681Asp	missense	Exon 11 of 11	NP_443116.2	Q96RL6-1
	SIGLEC11	NM_001135163.1		c.1754G>A	p.Gly585Asp	missense	Exon 10 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.2042G>A	p.Gly681Asp	missense	Exon 11 of 11	ENSP00000412361.2	Q96RL6-1
	SIGLEC11	ENST00000426971.2	TSL:1	c.1754G>A	p.Gly585Asp	missense	Exon 10 of 10	ENSP00000398891.2	Q96RL6-2
	ENSG00000269179	ENST00000451973.1	TSL:2	n.*77+1866G>A		intron	N/A	ENSP00000391489.1	H7BZU6

Frequencies

GnomAD3 genomes AF: 0.000230 AC: 35 AN: 152054 Hom.: 1 Cov.: 31

Gnomad AFR AF: 0.000846

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000471 AC: 10 AN: 212364 AF XY: 0.0000347

Gnomad AFR exome AF: 0.000666

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000222 AC: 31 AN: 1393612 Hom.: 0 Cov.: 30 AF XY: 0.0000233 AC XY: 16 AN XY: 687712

African (AFR) AF: 0.000872 AC: 27 AN: 30964

American (AMR) AF: 0.00 AC: 0 AN: 35120

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23030

East Asian (EAS) AF: 0.00 AC: 0 AN: 37852

South Asian (SAS) AF: 0.00 AC: 0 AN: 77798

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51958

Middle Eastern (MID) AF: 0.000182 AC: 1 AN: 5484

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1074484

Other (OTH) AF: 0.0000527 AC: 3 AN: 56922

GnomAD4 genome AF: 0.000230 AC: 35 AN: 152054 Hom.: 1 Cov.: 31 AF XY: 0.000323 AC XY: 24 AN XY: 74276

African (AFR) AF: 0.000846 AC: 35 AN: 41368

American (AMR) AF: 0.00 AC: 0 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.00 AC: 0 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67986

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.000152 Hom.: 0

Bravo AF: 0.000317

ESP6500AA AF: 0.000454 AC: 2

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000577 AC: 7

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	-0.53	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	1.5
DANN	Benign	0.94
DEOGEN2	Benign	0.0012	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.0031	N
LIST_S2	Benign	0.53	T
M_CAP	Benign	0.0040	T
MetaRNN	Benign	0.034	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	1.1	L
PhyloP100		-2.5
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.28	N
REVEL	Benign	0.062
Sift	Benign	0.11	T
Sift4G	Uncertain	0.036	D
Polyphen		0.15	B
Vest4		0.077
MVP		0.33
MPC		0.069
ClinPred		0.069	T
GERP RS		-5.4
Varity_R		0.040
gMVP		0.29
Mutation Taster		=98/2	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: rs373704230; hg19: chr19-50453282;