NM_033130.5:c.1498G>C

Variant names:

• chr19-51414941-C-G
• NM_033130.5:c.1498G>C
• SIGLEC10 p.Gly500Arg

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_033130.5(SIGLEC10):​c.1498G>C​(p.Gly500Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SIGLEC10 NM_033130.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.701
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033130.5. 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
	SIGLEC10	NM_033130.5	MANE Select	c.1498G>C	p.Gly500Arg	missense	Exon 8 of 11	NP_149121.2
	SIGLEC10	NM_001171156.2		c.1324G>C	p.Gly442Arg	missense	Exon 8 of 11	NP_001164627.1	Q96LC7-3
	SIGLEC10	NM_001171157.2		c.1330+240G>C		intron	N/A	NP_001164628.1	Q96LC7-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SIGLEC10	ENST00000339313.10	TSL:1 MANE Select	c.1498G>C	p.Gly500Arg	missense	Exon 8 of 11	ENSP00000345243.4	Q96LC7-1
	SIGLEC10	ENST00000439889.6	TSL:1	c.1324G>C	p.Gly442Arg	missense	Exon 8 of 11	ENSP00000389132.2	Q96LC7-3
	SIGLEC10	ENST00000353836.9	TSL:1	c.1330+240G>C		intron	N/A	ENSP00000342389.5	Q96LC7-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.34
BayesDel_addAF	Uncertain	0.027	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	20
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.58	D
Eigen	Benign	-0.088
Eigen_PC	Benign	-0.25
FATHMM_MKL	Benign	0.64	D
LIST_S2	Benign	0.74	T
M_CAP	Pathogenic	0.46	D
MetaRNN	Uncertain	0.65	D
MetaSVM	Uncertain	0.21	D
MutationAssessor	Pathogenic	3.0	M
PhyloP100		0.70
PrimateAI	Benign	0.43	T
PROVEAN	Pathogenic	-5.7	D
REVEL	Uncertain	0.41
Sift	Uncertain	0.015	D
Sift4G	Uncertain	0.011	D
Varity_R		0.34
gMVP		0.53
Mutation Taster		=85/15	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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr19-51918195;