NM_033130.5:c.668G>C

Variant names:

• chr19-51416704-C-G
• NM_033130.5:c.668G>C

Variant summary

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

The NM_033130.5(SIGLEC10):​c.668G>C​(p.Gly223Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SIGLEC10 NM_033130.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0230

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.668G>C	p.Gly223Ala	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.668G>C	p.Gly223Ala	missense_variant	Exon 3 of 11	1	NM_033130.5	ENSP00000345243.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 93

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 13, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.668G>C (p.G223A) alteration is located in exon 3 (coding exon 3) of the SIGLEC10 gene. This alteration results from a G to C substitution at nucleotide position 668, causing the glycine (G) at amino acid position 223 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.042	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	16
DANN	Benign	0.97
DEOGEN2	Uncertain	0.50	.;.;.;.;.;.;T;.
Eigen	Benign	-0.46
Eigen_PC	Benign	-0.73
FATHMM_MKL	Benign	0.028	N
LIST_S2	Uncertain	0.90	D;D;D;D;D;D;D;D
M_CAP	Benign	0.025	D
MetaRNN	Uncertain	0.43	T;T;T;T;T;T;T;T
MetaSVM	Uncertain	-0.24	T
MutationAssessor	Uncertain	2.5	.;M;.;.;.;.;M;.
PrimateAI	Benign	0.29	T
PROVEAN	Uncertain	-3.9	D;D;D;D;D;D;D;D
REVEL	Uncertain	0.30
Sift	Uncertain	0.0050	D;D;T;D;D;T;D;D
Sift4G	Uncertain	0.043	D;D;D;D;D;T;D;.
Polyphen		0.94	P;D;.;D;.;P;P;.
Vest4		0.24
MutPred		0.56		.;Gain of MoRF binding (P = 0.122);.;Gain of MoRF binding (P = 0.122);.;.;Gain of MoRF binding (P = 0.122);.;
MVP		0.81
ClinPred		0.71	D
GERP RS		-1.9
Varity_R		0.11
gMVP		0.30

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-51919958;