rs61741677

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr19-51416744-T-C
• chr19-51416744-T-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_033130.5(SIGLEC10):​c.628A>G​(p.Asn210Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.116 in 1,613,674 control chromosomes in the GnomAD database, including 11,657 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N210H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.094 (835 hom., cov: 32)
  • Exomes 𝑓: 0.12 (10822 hom.)
• Consequence: SIGLEC10 NM_033130.5 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.004534751).
• BP6: Variant 19-51416744-T-C is Benign according to our data. Variant chr19-51416744-T-C is described in ClinVar as Benign. ClinVar VariationId is 773360.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.136 is higher than 0.05.

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>G	p.Asn210Asp	missense	Exon 3 of 11	NP_149121.2
	SIGLEC10	NM_001171156.2		c.454A>G	p.Asn152Asp	missense	Exon 3 of 11	NP_001164627.1	Q96LC7-3
	SIGLEC10	NM_001171157.2		c.628A>G	p.Asn210Asp	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>G	p.Asn210Asp	missense	Exon 3 of 11	ENSP00000345243.4	Q96LC7-1
	SIGLEC10	ENST00000439889.6	TSL:1	c.454A>G	p.Asn152Asp	missense	Exon 3 of 11	ENSP00000389132.2	Q96LC7-3
	SIGLEC10	ENST00000353836.9	TSL:1	c.628A>G	p.Asn210Asp	missense	Exon 3 of 10	ENSP00000342389.5	Q96LC7-2

Frequencies

GnomAD3 genomes AF: 0.0938 AC: 14252 AN: 152006 Hom.: 835 Cov.: 32

Gnomad AFR AF: 0.0355

Gnomad AMI AF: 0.152

Gnomad AMR AF: 0.0788

Gnomad ASJ AF: 0.110

Gnomad EAS AF: 0.0450

Gnomad SAS AF: 0.144

Gnomad FIN AF: 0.138

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.124

Gnomad OTH AF: 0.101

GnomAD2 exomes AF: 0.105 AC: 25595 AN: 243034 AF XY: 0.111

Gnomad AFR exome AF: 0.0327

Gnomad AMR exome AF: 0.0595

Gnomad ASJ exome AF: 0.107

Gnomad EAS exome AF: 0.0473

Gnomad FIN exome AF: 0.134

Gnomad NFE exome AF: 0.123

Gnomad OTH exome AF: 0.110

GnomAD4 exome AF: 0.118 AC: 172329 AN: 1461550 Hom.: 10822 Cov.: 100 AF XY: 0.119 AC XY: 86460 AN XY: 727052

African (AFR) AF: 0.0297 AC: 990 AN: 33348

American (AMR) AF: 0.0587 AC: 2625 AN: 44686

Ashkenazi Jewish (ASJ) AF: 0.101 AC: 2641 AN: 26134

East Asian (EAS) AF: 0.0541 AC: 2149 AN: 39698

South Asian (SAS) AF: 0.130 AC: 11193 AN: 86236

European-Finnish (FIN) AF: 0.130 AC: 6961 AN: 53412

Middle Eastern (MID) AF: 0.103 AC: 595 AN: 5766

European-Non Finnish (NFE) AF: 0.125 AC: 138545 AN: 1111888

Other (OTH) AF: 0.110 AC: 6630 AN: 60382

GnomAD4 genome AF: 0.0937 AC: 14254 AN: 152124 Hom.: 835 Cov.: 32 AF XY: 0.0947 AC XY: 7039 AN XY: 74364

African (AFR) AF: 0.0354 AC: 1468 AN: 41474

American (AMR) AF: 0.0787 AC: 1203 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.110 AC: 381 AN: 3468

East Asian (EAS) AF: 0.0453 AC: 234 AN: 5166

South Asian (SAS) AF: 0.145 AC: 700 AN: 4820

European-Finnish (FIN) AF: 0.138 AC: 1460 AN: 10598

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.124 AC: 8426 AN: 67984

Other (OTH) AF: 0.100 AC: 212 AN: 2114

Alfa AF: 0.106 Hom.: 591

Bravo AF: 0.0855

ESP6500AA AF: 0.0363 AC: 160

ESP6500EA AF: 0.114 AC: 984

ExAC AF: 0.105 AC: 12736

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.055
BayesDel_addAF	Benign	-0.60	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	0.053
DANN	Benign	0.56
DEOGEN2	Benign	0.089	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.00068	N
LIST_S2	Benign	0.22	T
MetaRNN	Benign	0.0045	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-0.65	N
PhyloP100		-1.3
PrimateAI	Benign	0.23	T
PROVEAN	Benign	0.44	N
REVEL	Benign	0.18
Sift	Benign	1.0	T
Sift4G	Benign	0.58	T
Polyphen		0.0	B
Vest4		0.093
ClinPred		0.000019	T
GERP RS		-0.23
Varity_R		0.030
gMVP		0.19
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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; COSMIC: COSV59479311; COSMIC: COSV59479311;