rs202177835

Variant names:

• chr19-51416956-A-G
• rs202177835
• NM_033130.5:c.422-6T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_033130.5(SIGLEC10):​c.422-6T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00322 in 1,607,546 control chromosomes in the GnomAD database, including 42 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0096 (16 hom., cov: 32)
  • Exomes 𝑓: 0.0026 (26 hom.)
• Consequence: SIGLEC10 NM_033130.5 splice_region, intron
• Scores: Splicing: ADA: 0.00006613
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.451
• Publications: 4 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 (BayesDel_noAF=-0.88).
• BP6: Variant 19-51416956-A-G is Benign according to our data. Variant chr19-51416956-A-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 775584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00958 (1458/152200) while in subpopulation AFR AF = 0.0258 (1073/41536). AF 95% confidence interval is 0.0245. There are 16 homozygotes in GnomAd4. There are 699 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 16 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.422-6T>C		splice_region intron	N/A	NP_149121.2
	SIGLEC10	NM_001171156.2		c.421+126T>C		intron	N/A	NP_001164627.1	Q96LC7-3
	SIGLEC10	NM_001171157.2		c.422-6T>C		splice_region intron	N/A	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.422-6T>C		splice_region intron	N/A	ENSP00000345243.4	Q96LC7-1
	SIGLEC10	ENST00000439889.6	TSL:1	c.421+126T>C		intron	N/A	ENSP00000389132.2	Q96LC7-3
	SIGLEC10	ENST00000353836.9	TSL:1	c.422-6T>C		splice_region intron	N/A	ENSP00000342389.5	Q96LC7-2

Frequencies

GnomAD3 genomes AF: 0.00946 AC: 1438 AN: 152082 Hom.: 12 Cov.: 32

Gnomad AFR AF: 0.0257

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00720

Gnomad ASJ AF: 0.0179

Gnomad EAS AF: 0.0120

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00153

Gnomad OTH AF: 0.0144

GnomAD2 exomes AF: 0.00169 AC: 418 AN: 247546 AF XY: 0.00152

Gnomad AFR exome AF: 0.0110

Gnomad AMR exome AF: 0.00149

Gnomad ASJ exome AF: 0.00314

Gnomad EAS exome AF: 0.00569

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000393

Gnomad OTH exome AF: 0.00183

GnomAD4 exome AF: 0.00255 AC: 3714 AN: 1455346 Hom.: 26 Cov.: 101 AF XY: 0.00251 AC XY: 1815 AN XY: 723422

African (AFR) AF: 0.0280 AC: 934 AN: 33320

American (AMR) AF: 0.00327 AC: 145 AN: 44372

Ashkenazi Jewish (ASJ) AF: 0.0136 AC: 347 AN: 25602

East Asian (EAS) AF: 0.0152 AC: 601 AN: 39656

South Asian (SAS) AF: 0.000222 AC: 19 AN: 85556

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53078

Middle Eastern (MID) AF: 0.0152 AC: 87 AN: 5718

European-Non Finnish (NFE) AF: 0.00109 AC: 1204 AN: 1107980

Other (OTH) AF: 0.00628 AC: 377 AN: 60064

GnomAD4 genome AF: 0.00958 AC: 1458 AN: 152200 Hom.: 16 Cov.: 32 AF XY: 0.00939 AC XY: 699 AN XY: 74418

African (AFR) AF: 0.0258 AC: 1073 AN: 41536

American (AMR) AF: 0.00719 AC: 110 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0179 AC: 62 AN: 3468

East Asian (EAS) AF: 0.0120 AC: 62 AN: 5160

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.00153 AC: 104 AN: 67994

Other (OTH) AF: 0.0204 AC: 43 AN: 2110

Alfa AF: 0.00385 Hom.: 4

Bravo AF: 0.0102

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.8
DANN	Benign	0.70
PhyloP100		-0.45
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000066
dbscSNV1_RF	Benign	0.034
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: rs202177835; hg19: chr19-51920210;