chr19-51415981-T-C

Variant names:

• chr19-51415981-T-C
• rs201089294
• NM_033130.5:c.941A>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_033130.5(SIGLEC10):​c.941A>G​(p.Lys314Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00737 in 1,599,404 control chromosomes in the GnomAD database, including 112 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 Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0087 (10 hom., cov: 32)
  • Exomes 𝑓: 0.0072 (102 hom.)
• Consequence: SIGLEC10 NM_033130.5 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0290
• 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: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.004564494).
• BP6: Variant 19-51415981-T-C is Benign according to our data. Variant chr19-51415981-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 2650375.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 10 AR gene

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.941A>G	p.Lys314Arg	missense	Exon 5 of 11	NP_149121.2
	SIGLEC10	NM_001171156.2		c.767A>G	p.Lys256Arg	missense	Exon 5 of 11	NP_001164627.1	Q96LC7-3
	SIGLEC10	NM_001171157.2		c.941A>G	p.Lys314Arg	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.941A>G	p.Lys314Arg	missense	Exon 5 of 11	ENSP00000345243.4	Q96LC7-1
	SIGLEC10	ENST00000439889.6	TSL:1	c.767A>G	p.Lys256Arg	missense	Exon 5 of 11	ENSP00000389132.2	Q96LC7-3
	SIGLEC10	ENST00000353836.9	TSL:1	c.941A>G	p.Lys314Arg	missense	Exon 5 of 10	ENSP00000342389.5	Q96LC7-2

Frequencies

GnomAD3 genomes AF: 0.00874 AC: 1328 AN: 151860 Hom.: 10 Cov.: 32

Gnomad AFR AF: 0.00293

Gnomad AMI AF: 0.0340

Gnomad AMR AF: 0.00459

Gnomad ASJ AF: 0.00404

Gnomad EAS AF: 0.000582

Gnomad SAS AF: 0.00561

Gnomad FIN AF: 0.0117

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0134

Gnomad OTH AF: 0.0120

GnomAD2 exomes AF: 0.00414 AC: 1029 AN: 248786 AF XY: 0.00422

Gnomad AFR exome AF: 0.00136

Gnomad AMR exome AF: 0.00296

Gnomad ASJ exome AF: 0.00160

Gnomad EAS exome AF: 0.000218

Gnomad FIN exome AF: 0.00554

Gnomad NFE exome AF: 0.00592

Gnomad OTH exome AF: 0.00460

GnomAD4 exome AF: 0.00723 AC: 10459 AN: 1447426 Hom.: 102 Cov.: 37 AF XY: 0.00712 AC XY: 5125 AN XY: 720088

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00201 AC: 67 AN: 33408

American (AMR) AF: 0.00294 AC: 131 AN: 44578

Ashkenazi Jewish (ASJ) AF: 0.00177 AC: 46 AN: 26056

East Asian (EAS) AF: 0.000504 AC: 20 AN: 39690

South Asian (SAS) AF: 0.00342 AC: 294 AN: 85980

European-Finnish (FIN) AF: 0.0114 AC: 606 AN: 53026

Middle Eastern (MID) AF: 0.00971 AC: 52 AN: 5356

European-Non Finnish (NFE) AF: 0.00800 AC: 8797 AN: 1099462

Other (OTH) AF: 0.00745 AC: 446 AN: 59870

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.00874 AC: 1328 AN: 151978 Hom.: 10 Cov.: 32 AF XY: 0.00828 AC XY: 615 AN XY: 74280

African (AFR) AF: 0.00292 AC: 121 AN: 41482

American (AMR) AF: 0.00458 AC: 70 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00404 AC: 14 AN: 3468

East Asian (EAS) AF: 0.000583 AC: 3 AN: 5142

South Asian (SAS) AF: 0.00561 AC: 27 AN: 4812

European-Finnish (FIN) AF: 0.0117 AC: 124 AN: 10590

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.0134 AC: 910 AN: 67890

Other (OTH) AF: 0.0119 AC: 25 AN: 2106

Alfa AF: 0.00678 Hom.: 7

ExAC AF: 0.00799 AC: 970

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.52	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	3.8
DANN	Benign	0.84
DEOGEN2	Benign	0.079	T
Eigen	Benign	-0.94
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.0086	N
LIST_S2	Benign	0.12	T
MetaRNN	Benign	0.0046	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.66	N
PhyloP100		-0.029
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.072
Sift	Benign	0.39	T
Sift4G	Benign	0.31	T
Polyphen		0.18	B
Vest4		0.074
MVP		0.25
ClinPred		0.0076	T
GERP RS		-1.6
Varity_R		0.092
gMVP		0.16
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs201089294; hg19: chr19-51919235; COSMIC: COSV59480351; COSMIC: COSV59480351;