rs1568501652

Variant names:

• chr19-51416686-G-A
• rs1568501652
• NM_033130.5:c.686C>T

Your query was ambiguous. Multiple possible variants found:

• chr19-51416686-G-A
• chr19-51416686-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_033130.5(SIGLEC10):​c.686C>T​(p.Thr229Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,638 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 0.251

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-AS1 (HGNC:40719): (SIGLEC10 antisense RNA 1)

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SIGLEC10	NM_033130.5	c.686C>T	p.Thr229Ile	missense_variant	Exon 3 of 11	ENST00000339313.10	NP_149121.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SIGLEC10	ENST00000339313.10	c.686C>T	p.Thr229Ile	missense_variant	Exon 3 of 11	1	NM_033130.5	ENSP00000345243.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461638 Hom.: 0 Cov.: 52 AF XY: 0.00 AC XY: 0 AN XY: 727124

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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: 0.0000166

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.40
BayesDel_addAF	Uncertain	0.086	D
BayesDel_noAF	Benign	-0.11
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.61	.;.;.;.;.;.;D;.
Eigen	Benign	-0.059
Eigen_PC	Benign	-0.29
FATHMM_MKL	Benign	0.074	N
LIST_S2	Benign	0.71	T;T;T;T;T;T;T;T
M_CAP	Uncertain	0.14	D
MetaRNN	Uncertain	0.44	T;T;T;T;T;T;T;T
MetaSVM	Uncertain	0.11	D
MutationAssessor	Uncertain	2.7	.;M;.;.;.;.;M;.
PrimateAI	Benign	0.43	T
PROVEAN	Pathogenic	-5.1	D;D;D;D;D;D;D;D
REVEL	Benign	0.14
Sift	Uncertain	0.0050	D;D;D;D;D;D;D;D
Sift4G	Benign	0.10	T;D;D;D;T;D;D;.
Polyphen		1.0	D;D;.;D;.;D;D;.
Vest4		0.70
MutPred		0.62		.;Loss of phosphorylation at T229 (P = 0.0233);.;Loss of phosphorylation at T229 (P = 0.0233);.;.;Loss of phosphorylation at T229 (P = 0.0233);.;
MVP		0.90
ClinPred		0.81	D
GERP RS		3.6
Varity_R		0.19
gMVP		0.54

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: rs1568501652; hg19: chr19-51919940;