19-51415978-G-C

Variant names:

• chr19-51415978-G-C
• rs543398977
• NM_033130.5:c.944C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_033130.5(SIGLEC10):​c.944C>G​(p.Ala315Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,134 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A315D) has been classified as Uncertain significance.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: SIGLEC10 NM_033130.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.32
• Publications: 2 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18694782).

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.944C>G	p.Ala315Gly	missense	Exon 5 of 11	NP_149121.2
	SIGLEC10	NM_001171156.2		c.770C>G	p.Ala257Gly	missense	Exon 5 of 11	NP_001164627.1	Q96LC7-3
	SIGLEC10	NM_001171157.2		c.944C>G	p.Ala315Gly	missense	Exon 5 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.944C>G	p.Ala315Gly	missense	Exon 5 of 11	ENSP00000345243.4	Q96LC7-1
	SIGLEC10	ENST00000439889.6	TSL:1	c.770C>G	p.Ala257Gly	missense	Exon 5 of 11	ENSP00000389132.2	Q96LC7-3
	SIGLEC10	ENST00000353836.9	TSL:1	c.944C>G	p.Ala315Gly	missense	Exon 5 of 10	ENSP00000342389.5	Q96LC7-2

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152134 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 37

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152134 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74304

African (AFR) AF: 0.0000241 AC: 1 AN: 41452

American (AMR) AF: 0.00 AC: 0 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5166

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68004

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	20
DANN	Uncertain	0.98
DEOGEN2	Benign	0.11	T
Eigen	Benign	-0.36
Eigen_PC	Benign	-0.58
FATHMM_MKL	Benign	0.030	N
LIST_S2	Benign	0.57	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	2.0	M
PhyloP100		1.3
PrimateAI	Benign	0.34	T
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.047
Sift	Benign	0.071	T
Sift4G	Benign	0.30	T
Polyphen		0.94	P
Vest4		0.12
MutPred		0.40		Loss of sheet (P = 0.0817)
MVP		0.53
ClinPred		0.39	T
GERP RS		0.71
Varity_R		0.14
gMVP		0.21
Mutation Taster		=90/10	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: rs543398977; hg19: chr19-51919232;