19-51415977-A-G

Variant names:

• chr19-51415977-A-G
• rs112584540
• NM_033130.5:c.945T>C

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_033130.5(SIGLEC10):​c.945T>C​(p.Ala315Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00691 in 1,597,556 control chromosomes in the GnomAD database, including 114 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0089 (9 hom., cov: 32)
  • Exomes 𝑓: 0.0067 (105 hom.)
• Consequence: SIGLEC10 NM_033130.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.29
• Publications: 1 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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BP6: Variant 19-51415977-A-G is Benign according to our data. Variant chr19-51415977-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2650374.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-2.29 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 9 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.945T>C	p.Ala315Ala	synonymous	Exon 5 of 11	NP_149121.2
	SIGLEC10	NM_001171156.2		c.771T>C	p.Ala257Ala	synonymous	Exon 5 of 11	NP_001164627.1	Q96LC7-3
	SIGLEC10	NM_001171157.2		c.945T>C	p.Ala315Ala	synonymous	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.945T>C	p.Ala315Ala	synonymous	Exon 5 of 11	ENSP00000345243.4	Q96LC7-1
	SIGLEC10	ENST00000439889.6	TSL:1	c.771T>C	p.Ala257Ala	synonymous	Exon 5 of 11	ENSP00000389132.2	Q96LC7-3
	SIGLEC10	ENST00000353836.9	TSL:1	c.945T>C	p.Ala315Ala	synonymous	Exon 5 of 10	ENSP00000342389.5	Q96LC7-2

Frequencies

GnomAD3 genomes AF: 0.00886 AC: 1346 AN: 151888 Hom.: 9 Cov.: 32

Gnomad AFR AF: 0.00295

Gnomad AMI AF: 0.0340

Gnomad AMR AF: 0.00518

Gnomad ASJ AF: 0.00403

Gnomad EAS AF: 0.000583

Gnomad SAS AF: 0.00602

Gnomad FIN AF: 0.0116

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0135

Gnomad OTH AF: 0.0125

GnomAD2 exomes AF: 0.00420 AC: 1045 AN: 248860 AF XY: 0.00430

Gnomad AFR exome AF: 0.00142

Gnomad AMR exome AF: 0.00314

Gnomad ASJ exome AF: 0.00140

Gnomad EAS exome AF: 0.000217

Gnomad FIN exome AF: 0.00591

Gnomad NFE exome AF: 0.00593

Gnomad OTH exome AF: 0.00444

GnomAD4 exome AF: 0.00671 AC: 9698 AN: 1445550 Hom.: 105 Cov.: 37 AF XY: 0.00666 AC XY: 4789 AN XY: 719212

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

African (AFR) AF: 0.00198 AC: 66 AN: 33402

American (AMR) AF: 0.00312 AC: 139 AN: 44528

Ashkenazi Jewish (ASJ) AF: 0.00177 AC: 46 AN: 26060

East Asian (EAS) AF: 0.000529 AC: 21 AN: 39686

South Asian (SAS) AF: 0.00340 AC: 292 AN: 85954

European-Finnish (FIN) AF: 0.0115 AC: 611 AN: 53024

Middle Eastern (MID) AF: 0.00972 AC: 52 AN: 5352

European-Non Finnish (NFE) AF: 0.00733 AC: 8041 AN: 1097734

Other (OTH) AF: 0.00719 AC: 430 AN: 59810

⚠️ 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: 0.00885 AC: 1346 AN: 152006 Hom.: 9 Cov.: 32 AF XY: 0.00841 AC XY: 625 AN XY: 74296

African (AFR) AF: 0.00294 AC: 122 AN: 41506

American (AMR) AF: 0.00518 AC: 79 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.00403 AC: 14 AN: 3470

East Asian (EAS) AF: 0.000584 AC: 3 AN: 5136

South Asian (SAS) AF: 0.00602 AC: 29 AN: 4816

European-Finnish (FIN) AF: 0.0116 AC: 123 AN: 10604

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

European-Non Finnish (NFE) AF: 0.0135 AC: 916 AN: 67904

Other (OTH) AF: 0.0123 AC: 26 AN: 2106

Alfa AF: 0.00770 Hom.: 7

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
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.14
DANN	Benign	0.43
PhyloP100		-2.3
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs112584540; hg19: chr19-51919231;