NM_033130.5:c.1605G>C

Variant names:

• chr19-51414834-C-G
• rs145650287
• NM_033130.5:c.1605G>C

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Moderate BP6_Very_Strong BP7 BS2

The NM_033130.5(SIGLEC10):​c.1605G>C​(p.Leu535Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00526 in 1,613,712 control chromosomes in the GnomAD database, including 38 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0045 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0053 (36 hom.)
• Consequence: SIGLEC10 NM_033130.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.40
• Publications: 0 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-AS2 (HGNC:40718): (SIGLEC10 antisense RNA 2)

ACMG classification

Our verdict: Benign. The variant received -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BP6: Variant 19-51414834-C-G is Benign according to our data. Variant chr19-51414834-C-G is described in ClinVar as Benign. ClinVar VariationId is 770811.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=2.4 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 2 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.1605G>C	p.Leu535Leu	synonymous	Exon 8 of 11	NP_149121.2
	SIGLEC10	NM_001171156.2		c.1431G>C	p.Leu477Leu	synonymous	Exon 8 of 11	NP_001164627.1	Q96LC7-3
	SIGLEC10	NM_001171157.2		c.1331-319G>C		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.1605G>C	p.Leu535Leu	synonymous	Exon 8 of 11	ENSP00000345243.4	Q96LC7-1
	SIGLEC10	ENST00000439889.6	TSL:1	c.1431G>C	p.Leu477Leu	synonymous	Exon 8 of 11	ENSP00000389132.2	Q96LC7-3
	SIGLEC10	ENST00000353836.9	TSL:1	c.1331-319G>C		intron	N/A	ENSP00000342389.5	Q96LC7-2

Frequencies

GnomAD3 genomes AF: 0.00451 AC: 687 AN: 152214 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.000772

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00111

Gnomad ASJ AF: 0.00662

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000827

Gnomad FIN AF: 0.0171

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00613

Gnomad OTH AF: 0.00526

GnomAD2 exomes AF: 0.00570 AC: 1406 AN: 246738 AF XY: 0.00590

Gnomad AFR exome AF: 0.000778

Gnomad AMR exome AF: 0.00189

Gnomad ASJ exome AF: 0.00840

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0197

Gnomad NFE exome AF: 0.00684

Gnomad OTH exome AF: 0.00694

GnomAD4 exome AF: 0.00534 AC: 7797 AN: 1461380 Hom.: 36 Cov.: 31 AF XY: 0.00532 AC XY: 3871 AN XY: 727032

African (AFR) AF: 0.000927 AC: 31 AN: 33450

American (AMR) AF: 0.00180 AC: 80 AN: 44556

Ashkenazi Jewish (ASJ) AF: 0.00961 AC: 251 AN: 26118

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.000835 AC: 72 AN: 86220

European-Finnish (FIN) AF: 0.0160 AC: 855 AN: 53340

Middle Eastern (MID) AF: 0.0111 AC: 64 AN: 5764

European-Non Finnish (NFE) AF: 0.00554 AC: 6165 AN: 1111854

Other (OTH) AF: 0.00462 AC: 279 AN: 60382

GnomAD4 genome AF: 0.00449 AC: 684 AN: 152332 Hom.: 2 Cov.: 32 AF XY: 0.00467 AC XY: 348 AN XY: 74484

African (AFR) AF: 0.000769 AC: 32 AN: 41592

American (AMR) AF: 0.00111 AC: 17 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00662 AC: 23 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4830

European-Finnish (FIN) AF: 0.0171 AC: 181 AN: 10612

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.00613 AC: 417 AN: 68024

Other (OTH) AF: 0.00473 AC: 10 AN: 2114

Alfa AF: 0.00576 Hom.: 2

Bravo AF: 0.00360

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.00551

EpiControl AF: 0.00652

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
BayesDel_noAF	Benign	-0.44
CADD	Benign	8.7
DANN	Benign	0.63
PhyloP100		2.4
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs145650287; hg19: chr19-51918088; COSMIC: COSV59484221; COSMIC: COSV59484221;