chr19-51413809-G-C

Variant names:

• chr19-51413809-G-C
• rs775153809
• NM_033130.5:c.1724C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_033130.5(SIGLEC10):​c.1724C>G​(p.Pro575Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,790 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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. P575L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SIGLEC10 NM_033130.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0600
• 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]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05104944).

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.1724C>G	p.Pro575Arg	missense	Exon 10 of 11	NP_149121.2
	SIGLEC10	NM_001171156.2		c.1550C>G	p.Pro517Arg	missense	Exon 10 of 11	NP_001164627.1	Q96LC7-3
	SIGLEC10	NM_001171157.2		c.1439C>G	p.Pro480Arg	missense	Exon 9 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.1724C>G	p.Pro575Arg	missense	Exon 10 of 11	ENSP00000345243.4	Q96LC7-1
	SIGLEC10	ENST00000439889.6	TSL:1	c.1550C>G	p.Pro517Arg	missense	Exon 10 of 11	ENSP00000389132.2	Q96LC7-3
	SIGLEC10	ENST00000353836.9	TSL:1	c.1439C>G	p.Pro480Arg	missense	Exon 9 of 10	ENSP00000342389.5	Q96LC7-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461790 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727212

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53410

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111930

Other (OTH) AF: 0.00 AC: 0 AN: 60392

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	0.15
DANN	Benign	0.51
DEOGEN2	Benign	0.079	T
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.0014	N
LIST_S2	Benign	0.55	T
M_CAP	Benign	0.0026	T
MetaRNN	Benign	0.051	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-2.0	N
PhyloP100		-0.060
PrimateAI	Benign	0.21	T
PROVEAN	Benign	0.43	N
REVEL	Benign	0.11
Sift	Benign	0.78	T
Sift4G	Benign	0.81	T
Polyphen		0.0040	B
Vest4		0.11
MutPred		0.47		Gain of MoRF binding (P = 6e-04)
MVP		0.23
ClinPred		0.057	T
GERP RS		-0.52
Varity_R		0.030
gMVP		0.075
Mutation Taster		=96/4	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: rs775153809; hg19: chr19-51917063;