NM_033130.5:c.628A>C

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 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. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N210D) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SIGLEC10 NM_033130.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.32
• Publications: 16 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-AS1 (HGNC:40719): (SIGLEC10 antisense RNA 1)

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.628A>C	p.Asn210His	missense	Exon 3 of 11	NP_149121.2
	SIGLEC10	NM_001171156.2		c.454A>C	p.Asn152His	missense	Exon 3 of 11	NP_001164627.1	Q96LC7-3
	SIGLEC10	NM_001171157.2		c.628A>C	p.Asn210His	missense	Exon 3 of 10	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.628A>C	p.Asn210His	missense	Exon 3 of 11	ENSP00000345243.4	Q96LC7-1
	SIGLEC10	ENST00000439889.6	TSL:1	c.454A>C	p.Asn152His	missense	Exon 3 of 11	ENSP00000389132.2	Q96LC7-3
	SIGLEC10	ENST00000353836.9	TSL:1	c.628A>C	p.Asn210His	missense	Exon 3 of 10	ENSP00000342389.5	Q96LC7-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 100

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 591

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
Eigen	Benign	-0.96
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.019	N
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.081	D
MetaRNN	Uncertain	0.46	T
MetaSVM	Benign	-0.30	T
MutationAssessor	Benign	1.4	L
PhyloP100		-1.3
PrimateAI	Benign	0.23	T
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.28
Sift	Benign	0.074	T
Sift4G	Uncertain	0.039	D
Polyphen		0.89	P
Vest4		0.24
MutPred		0.70		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
Mutation Taster		=99/1	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: rs61741677; hg19: chr19-51919998;