NM_033130.5:c.688G>C

Variant names:

• chr19-51416684-C-G
• NM_033130.5:c.688G>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_033130.5(SIGLEC10):​c.688G>C​(p.Val230Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,544 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 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)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: SIGLEC10 NM_033130.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.983

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20953587).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SIGLEC10	NM_033130.5	c.688G>C	p.Val230Leu	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.688G>C	p.Val230Leu	missense_variant	Exon 3 of 11	1	NM_033130.5	ENSP00000345243.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461544 Hom.: 0 Cov.: 56 AF XY: 0.00000275 AC XY: 2 AN XY: 727082

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: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.33
BayesDel_addAF	Benign	0.0066	T
BayesDel_noAF	Benign	-0.23
CADD	Benign	14
DANN	Benign	0.96
DEOGEN2	Uncertain	0.50	.;.;.;.;.;.;D;.
Eigen	Benign	-0.55
Eigen_PC	Benign	-0.78
FATHMM_MKL	Benign	0.033	N
LIST_S2	Benign	0.62	T;T;T;T;T;T;T;T
M_CAP	Benign	0.077	D
MetaRNN	Benign	0.21	T;T;T;T;T;T;T;T
MetaSVM	Uncertain	-0.23	T
MutationAssessor	Uncertain	2.4	.;M;.;.;.;.;M;.
PrimateAI	Benign	0.36	T
PROVEAN	Uncertain	-2.4	N;D;N;N;D;N;D;D
REVEL	Benign	0.11
Sift	Benign	0.079	T;T;T;T;D;T;T;D
Sift4G	Benign	0.24	T;T;T;T;T;T;T;.
Polyphen		0.99	D;D;.;D;.;P;P;.
Vest4		0.27
MutPred		0.53		.;Loss of MoRF binding (P = 0.1385);.;Loss of MoRF binding (P = 0.1385);.;.;Loss of MoRF binding (P = 0.1385);.;
MVP		0.61
ClinPred		0.44	T
GERP RS		-2.3
Varity_R		0.12
gMVP		0.41

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: chr19-51919938;