rs545140583

Variant names:

• chr19-51414480-C-G
• rs545140583
• NM_033130.5:c.1651G>C

Your query was ambiguous. Multiple possible variants found:

• chr19-51414480-C-G
• chr19-51414480-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_033130.5(SIGLEC10):​c.1651G>C​(p.Gly551Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,778 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SIGLEC10 NM_033130.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.73

Genes affected

SIGLEC10 (HGNC:15620): (sialic acid binding Ig like lectin 10) SIGLECs are members of the immunoglobulin superfamily that are expressed on the cell surface. Most SIGLECs have 1 or more cytoplasmic immune receptor tyrosine-based inhibitory motifs, or ITIMs. SIGLECs are typically expressed on cells of the innate immune system, with the exception of the B-cell expressed SIGLEC6 (MIM 604405).[supplied by OMIM, Jul 2002]

SIGLEC10-AS2 (HGNC:40718): (SIGLEC10 antisense RNA 2)

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.819

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SIGLEC10	NM_033130.5	c.1651G>C	p.Gly551Arg	missense_variant	Exon 9 of 11	ENST00000339313.10	NP_149121.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SIGLEC10	ENST00000339313.10	c.1651G>C	p.Gly551Arg	missense_variant	Exon 9 of 11	1	NM_033130.5	ENSP00000345243.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251154 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135730

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461778 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 727168

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000224

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.47
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Pathogenic	0.15
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.65	.;.;.;.;.;.;D
Eigen	Uncertain	0.34
Eigen_PC	Benign	0.17
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.76	T;T;T;T;T;D;D
M_CAP	Uncertain	0.10	D
MetaRNN	Pathogenic	0.82	D;D;D;D;D;D;D
MetaSVM	Benign	-0.35	T
MutationAssessor	Pathogenic	2.9	.;.;.;.;.;.;M
PrimateAI	Benign	0.37	T
PROVEAN	Pathogenic	-6.4	D;D;D;D;D;D;D
REVEL	Uncertain	0.35
Sift	Uncertain	0.0020	D;D;D;D;D;D;D
Sift4G	Pathogenic	0.0010	D;D;D;D;D;D;D
Polyphen		1.0	D;D;.;D;.;P;D
Vest4		0.69
MutPred		0.53		.;.;.;.;.;.;Loss of glycosylation at T546 (P = 0.2304);
MVP		0.80
ClinPred		0.93	D
GERP RS		4.9
Varity_R		0.51
gMVP		0.58

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs545140583; hg19: chr19-51917734;