NM_033130.5:c.939G>A

Variant names:

• chr19-51415983-C-T
• rs199590261
• NM_033130.5:c.939G>A

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.939G>A​(p.Val313Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00751 in 1,600,040 control chromosomes in the GnomAD database, including 112 homozygotes. In-silico tool predicts 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: 0.0074 (102 hom.)
• Consequence: SIGLEC10 NM_033130.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.588
• 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=-0.81).
• BP6: Variant 19-51415983-C-T is Benign according to our data. Variant chr19-51415983-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2650376.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.588 with no splicing effect.
• 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.939G>A	p.Val313Val	synonymous	Exon 5 of 11	NP_149121.2
	SIGLEC10	NM_001171156.2		c.765G>A	p.Val255Val	synonymous	Exon 5 of 11	NP_001164627.1	Q96LC7-3
	SIGLEC10	NM_001171157.2		c.939G>A	p.Val313Val	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.939G>A	p.Val313Val	synonymous	Exon 5 of 11	ENSP00000345243.4	Q96LC7-1
	SIGLEC10	ENST00000439889.6	TSL:1	c.765G>A	p.Val255Val	synonymous	Exon 5 of 11	ENSP00000389132.2	Q96LC7-3
	SIGLEC10	ENST00000353836.9	TSL:1	c.939G>A	p.Val313Val	synonymous	Exon 5 of 10	ENSP00000342389.5	Q96LC7-2

Frequencies

GnomAD3 genomes AF: 0.00875 AC: 1330 AN: 152036 Hom.: 10 Cov.: 32

Gnomad AFR AF: 0.00295

Gnomad AMI AF: 0.0340

Gnomad AMR AF: 0.00459

Gnomad ASJ AF: 0.00403

Gnomad EAS AF: 0.000580

Gnomad SAS AF: 0.00559

Gnomad FIN AF: 0.0115

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0134

Gnomad OTH AF: 0.0120

GnomAD2 exomes AF: 0.00442 AC: 1101 AN: 248868 AF XY: 0.00451

Gnomad AFR exome AF: 0.00124

Gnomad AMR exome AF: 0.00313

Gnomad ASJ exome AF: 0.00209

Gnomad EAS exome AF: 0.000217

Gnomad FIN exome AF: 0.00568

Gnomad NFE exome AF: 0.00640

Gnomad OTH exome AF: 0.00493

GnomAD4 exome AF: 0.00738 AC: 10680 AN: 1447886 Hom.: 102 Cov.: 37 AF XY: 0.00725 AC XY: 5219 AN XY: 720304

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

African (AFR) AF: 0.00204 AC: 68 AN: 33410

American (AMR) AF: 0.00296 AC: 132 AN: 44576

Ashkenazi Jewish (ASJ) AF: 0.00188 AC: 49 AN: 26064

East Asian (EAS) AF: 0.000504 AC: 20 AN: 39692

South Asian (SAS) AF: 0.00347 AC: 298 AN: 85996

European-Finnish (FIN) AF: 0.0115 AC: 608 AN: 53026

Middle Eastern (MID) AF: 0.0103 AC: 55 AN: 5352

European-Non Finnish (NFE) AF: 0.00818 AC: 8993 AN: 1099882

Other (OTH) AF: 0.00763 AC: 457 AN: 59888

⚠️ 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: 1330 AN: 152154 Hom.: 10 Cov.: 32 AF XY: 0.00832 AC XY: 619 AN XY: 74398

African (AFR) AF: 0.00294 AC: 122 AN: 41540

American (AMR) AF: 0.00458 AC: 70 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00403 AC: 14 AN: 3472

East Asian (EAS) AF: 0.000581 AC: 3 AN: 5162

South Asian (SAS) AF: 0.00560 AC: 27 AN: 4822

European-Finnish (FIN) AF: 0.0115 AC: 122 AN: 10616

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

European-Non Finnish (NFE) AF: 0.0134 AC: 913 AN: 67940

Other (OTH) AF: 0.0118 AC: 25 AN: 2110

Alfa AF: 0.00681 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	-0.81
CADD	Benign	11
DANN	Benign	0.77
PhyloP100		0.59
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs199590261; hg19: chr19-51919237;