19-51416744-T-G

Variant names:

• chr19-51416744-T-G
• rs61741677
• NM_033130.5:c.628A>C

Variant summary

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

The NM_033130.5(SIGLEC10):​c.628A>C​(p.Asn210His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SIGLEC10 NM_033130.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.32

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.628A>C	p.Asn210His	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.628A>C	p.Asn210His	missense_variant	Exon 3 of 11	1	NM_033130.5	ENSP00000345243.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 100

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	10
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.50	.;.;.;.;.;.;D;.;T
Eigen	Benign	-0.96
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.019	N
LIST_S2	Benign	0.77	T;T;T;T;T;T;T;T;D
M_CAP	Benign	0.081	D
MetaRNN	Uncertain	0.46	T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.30	T
MutationAssessor	Benign	1.4	.;L;.;.;.;.;L;.;.
PrimateAI	Benign	0.23	T
PROVEAN	Uncertain	-2.4	N;D;N;D;D;N;N;N;D
REVEL	Benign	0.28
Sift	Benign	0.074	T;T;T;D;T;T;D;D;D
Sift4G	Uncertain	0.039	D;D;D;D;D;T;D;.;.
Polyphen		0.89	P;D;.;P;.;P;D;.;.
Vest4		0.24
MutPred		0.70		.;Loss of solvent accessibility (P = 0.0193);.;Loss of solvent accessibility (P = 0.0193);.;.;Loss of solvent accessibility (P = 0.0193);.;.;
MVP		0.76
ClinPred		0.59	D
GERP RS		-0.23
Varity_R		0.060
gMVP		0.30

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: rs61741677; hg19: chr19-51919998;